Medicine › Physiology

Biochemical effects in animals

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This cluster of papers explores the physiology and pathophysiology of carnosine, a dipeptide with antioxidant and neuroprotective properties. It covers topics such as the effects of ß-alanine supplementation on muscle carnosine, its role in diabetic nephropathy, exercise performance, and its potential in mitigating oxidative stress and aging-related processes.

Keywords

Carnosine; ß-Alanine Supplementation; Muscle Carnosine; Antioxidant; Neuroprotection; Diabetic Nephropathy; Exercise Performance; Histidine Dipeptides; Aging; Oxidative Stress

[27] The cyanogen bromide reaction

1967-01-01

Erhard Gross

Free Radicals and Brain Damage

1993-01-01

David S. Smith

PEPTIDES OBTAINED BY TRYPTIC HYDROLYSIS OF PERFORMIC ACID-OXIDIZED RIBONUCLEASE

1956-04-01

C.H.W. Hirs , Stanford Moore , William H. Stein

Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain.

1977-11-01

Masatoshi Inoue , Akira Kishimoto , Yoshimi Takai +1 more

was found in the soluble fraction of rat brain.Upon limited proteolysis by calcium-dependent protease occurring in the same tissue, the proenzyme was converted to an active protein kinase which could … was found in the soluble fraction of rat brain.Upon limited proteolysis by calcium-dependent protease occurring in the same tissue, the proenzyme was converted to an active protein kinase which could phosphorylate five species of histone fractions.Trypsin also catalyzed the conversion.

Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria

1989-05-01

Kimberly M. Broekemeier , Mary E. Dempsey , Douglas R. Pfeiffer

The immunosuppressive peptide cyclosporin A is a powerful inhibitor of the Ca2+-dependent permeability transition in rat liver mitochondria.When swelling is used to monitor the transition, the inhibitor is effective regardless … The immunosuppressive peptide cyclosporin A is a powerful inhibitor of the Ca2+-dependent permeability transition in rat liver mitochondria.When swelling is used to monitor the transition, the inhibitor is effective regardless of whether N-ethylmaleimide, H6+, WY-14643, t-butyl hydroperoxide, oxalacetate, rhein, phosphate, phosphoenolpyruvate, or ruthenium red plus uncoupler is used as the inducing agent.Twentyfive to fifty pmol/mg protein of cyclosporin A reduces the swelling response by 50% with complete inhibition obtained at about 150 pmol/mg protein.The compound, which does not inhibit Ca2+ uptake or mitochondrial phospholipase Az, is effective when added before or after the transition promoting agent.These findings, together with the shape of the inhibition dose-response curve, suggest that cyclosporin A essentially titrates a mitochondrial component which is present at 80-90 pmol/mg protein.It is proposed that this component is a solute unselective, regulated pore or a factor involved in controlling such a structure.Mitochondria from liver (e.g.Refs. 1 and 2), kidney (e.g.Refs. 3 and 4), heart (e.g.Refs.5-10), adrenal cortex (e.g.Refs.11 and 12), and other tissues can undergo a "permeability transition" whereby the inner membrane becomes permeable to ions and molecules of low to moderate molecular weight.The transition, which is readily reversible (13-16),' occurs when Ca2+ loading is followed or preceded by addition of a second agent, referred to as an inducing agent or a Ca2+releasing agent.Chemically, the inducing agents are surprisingly diverse.Sulfhydryl reagents (e.g.Refs. 1 and 2), peroxides (e.g. , intermediary metabolites (e.g. , heavy metals (e.g.Refs.23 and 24), and other toxins (e.g.Refs. 25 and 26) as well as several pharmacological agents (e.g.Refs.27 and 28) are included.We proposed that despite the chemical diversity, transition-inducing agents function by a common mechanism.Perturbation of a phospholipid acylation-deacylation cycle is seen as a central event leading to the transition (2, 18, 20, 29).The hypothesis is that Ca2+ increases cycle activity by stimulating the mitochondrial

Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.

1977-04-01

Harold O. Conn , Carroll M. Leevy , Z.R. Vlahcevic +4 more

ON TYROSINE AND TRYPTOPHANE DETERMINATIONS IN PROTEINS

1927-06-01

Otto Folin , Vintila Ciocalteu

The article summarizes research into the existing methods for the quantitative determination of tyrosine and tryptophane in proteins. Limitations to the accuracy of the Folin-Looney method (reaction of a phosphotungstic … The article summarizes research into the existing methods for the quantitative determination of tyrosine and tryptophane in proteins. Limitations to the accuracy of the Folin-Looney method (reaction of a phosphotungstic phosphomolybdic acid in a phenol solution, evaluated using colorimetry) have been solved by an improved method detailed in the text. The hydrolysis of proteinaceous material to allow chemical analysis of tryptophane has also been improved; the method is based on digestion with sodium hydroxide for 18-20 hours, followed by rapid neutralization and acidification with sulfuric acid. A more accurate test for tyrosine based on Millon's reaction has been developed; acidified mercuric sulfate solution is used to dissolve precipitated tyrosine and sodium nitrite is added to produce the colored product which is assessed colorimetrically. Two types of casein analyzed by these methods contained 1.4% tryptophane and 6.37-6.55% tyrosine. Tryptophane and tyrosine content of various materials were: casein 1.4%, 6.4-6.6%; egg albumin 1.3%, 4.0%; edestin 1.5%, 4.5%; gliadin 0.84%, 3.1%; zein 0.17%, 5.9%. A method for preparation of the pure mercuric sulfate reagent is described.

THE MECHANISM OF ACTION OF GLYOXALASE

1951-06-01

E. Racker

UPTAKE OF RADIOACTIVE ALANINE IN VITRO INTO THE PROTEINS OF RAT LIVER FRACTIONS

1952-04-01

Philip Siekevitz

γ-AMINOBUTYRIC ACID IN BRAIN: ITS FORMATION FROM GLUTAMIC ACID

1950-11-01

Eugene Roberts , Sam Frankel

Ca++ Uptake by Rat Kidney Mitochondria and Its Dependence on Respiration and Phosphorylation

1962-08-01

Frank D. Vasington , Jerome V. Murphy

Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides

1982-02-01

Fulvio Ursini , Matilde Maiorino , Marialuisa Valente +2 more

Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review

2014-10-30

Imen Belhadj Slimen , Taha Najar , Abdeljelil Ghram +3 more

In recent years there has been enormous interest in researching oxidative stress. Reactive oxygen species (ROS) are derived from the metabolism of oxygen as by-products of cell respiration, and are … In recent years there has been enormous interest in researching oxidative stress. Reactive oxygen species (ROS) are derived from the metabolism of oxygen as by-products of cell respiration, and are continuously produced in all aerobic organisms. Oxidative stress occurs as a consequence of an imbalance between ROS production and the available antioxidant defence against them. Nowadays, a variety of diseases and degenerative processes such as cancer, Alzheimer's and autoimmune diseases are mediated by oxidative stress. Heat stress was suggested to be an environmental factor responsible for stimulating ROS production because of similarities in responses observed following heat stress compared with that occurring following exposure to oxidative stress. This manuscript describes the main mitochondrial sources of ROS and the antioxidant defences involved to prevent oxidative damage in all the mitochondrial compartments. It also deals with discussions concerning the cytotoxic effect of heat stress, mitochondrial heat-induced alterations, as well as heat shock protein (HSP) expression as a defence mechanism.

Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options

2009-03-01

Bayani Uttara , Ajay Singh , Paolo Zamboni +1 more

Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced … Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimers disease, Parkinsons disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario. Keywords: ROS, oxidative stress, antioxidants, neurodegenerative diseases, rns, amyloid, catalase, phagocytes

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Chemistry of Visual Adaptation in the Rat

1960-10-01

John E. Dowling

Lipid stability in meat and meat products

1998-01-01

P.A. Morrissey , P. J. A. Sheehy , Karen Galvin +2 more

Interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide. Inactivation of the enzyme

1975-12-01

Ellen K. Hodgson , Irwin Fridovich

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of bovine erythrocyte superoxide dismutase with hydrogen peroxide. Inactivation of the enzymeEllen K. Hodgson and Irwin FridovichCite this: Biochemistry 1975, 14, 24, 5294–5299Publication Date (Print):December 1, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of bovine erythrocyte superoxide dismutase with hydrogen peroxide. Inactivation of the enzymeEllen K. Hodgson and Irwin FridovichCite this: Biochemistry 1975, 14, 24, 5294–5299Publication Date (Print):December 1, 1975Publication History Published online1 May 2002Published inissue 1 December 1975https://pubs.acs.org/doi/10.1021/bi00695a010https://doi.org/10.1021/bi00695a010research-articleACS PublicationsRequest reuse permissionsArticle Views1008Altmetric-Citations585LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Protein oxidation and aging

2006-01-01

Earl R. Stadtman

Organisms are constantly exposed to various forms of reactive oxygen species (ROS) that lead to oxidation of proteins, nucleic acids, and lipids. Protein oxidation can involve cleavage of the polypeptide … Organisms are constantly exposed to various forms of reactive oxygen species (ROS) that lead to oxidation of proteins, nucleic acids, and lipids. Protein oxidation can involve cleavage of the polypeptide chain, modification of amino acid side chains, and conversion of the protein to derivatives that are highly sensitive to proteolytic degradation. Unlike other types of modification (except cysteine oxidation), oxidation of methionine residues to methionine sulfoxide is reversible; thus, cyclic oxidation and reduction of methionine residues leads to consumption of ROS and thereby increases the resistance of proteins to oxidation. The importance of protein oxidation in aging is supported by the observation that levels of oxidized proteins increase with animal age. The age-related accumulation of oxidized proteins may reflect age-related increases in rates of ROS generation, decreases in antioxidant activities, or losses in the capacity to degrade oxidized proteins.

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The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma

1987-06-01

D. D. M. Wayner , Graham W. Burton , K. U. Ingold +2 more

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Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in Vivo using an inhibitor of the aromatic amino acid decarboxylase

1972-01-01

Arvid Carlsson , James N. Davis , W. Kehr +2 more

Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties

1986-07-01

R. K. Emaus , Ron Grunwald , John J. Lemasters

Review: Alzheimer's Amyloid β-Peptide-Associated Free Radical Oxidative Stress and Neurotoxicity

2000-06-01

S. Varadarajan , Servet Yatin , Marina Aksenova +1 more

Het mechanism of the protective action of glycerol against haemolysis by freezing and thawing

1953-01-01

J. E. Lovelock

The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat

1965-03-01

Douglas D. McGregor

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Antioxidative Properties of Histidine-Containing Peptides Designed from Peptide Fragments Found in the Digests of a Soybean Protein

1998-01-01

Hua-Ming Chen , Koji Muramoto , Fumio Yamauchi +2 more

The properties of 22 synthetic peptides containing histidine, which were designed on the basis of the antioxidative peptide (Leu-Leu-Pro-His-His) derived from proteolytic digests of a soybean protein, were examined with … The properties of 22 synthetic peptides containing histidine, which were designed on the basis of the antioxidative peptide (Leu-Leu-Pro-His-His) derived from proteolytic digests of a soybean protein, were examined with regard to their antioxidative activity against the peroxidation of linoleic acid and the scavenging effects on active oxygen and free radical species. The antioxidative activities of these peptides in an emulsion oxidation system using 2,2'-azobis(2-amidinopropane) dihydrochloride as a radical initiator correlated well within an aqueous system. Although the histidine-containing peptides had a quenching activity on singlet oxygen, they did not show antioxidative activity in an 2,2'-azobis(2,4-dimethylvaleronitrile)-induced oxidation system or scavenging effects on 1,1-diphenyl-2-picrylhydrazyl radical and superoxide. The metal-ion chelating activities and the hydrophobicities of these peptides showed no direct correlation with their antioxidative activities. Leu-Leu-Pro-His-His was modified with a hydroxyl radical in an aqueous ethanol system during the peroxidation of linoleic acid.

Antioxidant Activity of Peptides Obtained from Porcine Myofibrillar Proteins by Protease Treatment

2003-05-10

Ai Saiga , Soichi Tanabe , Toshihide Nishimura

Hydrolysates obtained from porcine myofibrillar proteins by protease treatment (papain or actinase E) exhibited high antioxidant activity in a linolenic acid peroxidation system induced by Fe2+. Hydrolysates produced by both … Hydrolysates obtained from porcine myofibrillar proteins by protease treatment (papain or actinase E) exhibited high antioxidant activity in a linolenic acid peroxidation system induced by Fe2+. Hydrolysates produced by both papain and actinase E showed higher activities at pH 7.1 than at pH 5.4. The antioxidant activity of the papain hydrolysate was almost the same as that of vitamin E at pH 7.0. These hydrolysates possessed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and chelating activity toward metal ions. Antioxidant peptides were separated from the papain hydrolysate by ion exchange chromatography. The acidic fraction obtained by this method exhibited higher activity than the neutral or basic fractions. Antioxidant peptides in the acidic fraction were isolated by high-performance liquid chromatography on an ODS column and shown to possess the structures DSGVT, IEAEGE, DAQEKLE, EELDNALN, and VPSIDDQEELM. The DAQEKLE peptide showed the highest activity among these peptides. Keywords: Antioxidant; papain; myofibrillar protein hydrolysate; peptide

Free amino acids and peptides as related to antioxidant properties in protein hydrolysates of mackerel (Scomber austriasicus)

2003-01-01

Hui-Chun Wu , Hua‐Ming Chen , Chyuan‐Yuan Shiau

Hydroxyl radical scavenging activity of compatible solutes

1989-01-01

Nicholas Smirnoff , Quinton J. Cumbes

Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity

2007-09-20

Vittorio Calabrese , Cesare Mancuso , Menotti Calvani +3 more

Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain.

1988-05-01

R. Kohen , Yumi Yamamoto , K C Cundy +1 more

Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of … Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radical-trapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle.

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Protons and Anaerobiosis

1983-03-25

Peter W. Hochachka , Thomas P. Mommsen

During oxygen limitation in animals, glucose can be fermented via several metabolic pathways varying in energetic efficiency and leading to various end products (such as lactate, alanopine, octopine, succinate, or … During oxygen limitation in animals, glucose can be fermented via several metabolic pathways varying in energetic efficiency and leading to various end products (such as lactate, alanopine, octopine, succinate, or propionate). Because of opposite pH dependencies of proton production by fermentation and by hydrolysis of adenosine triphosphate formed in the fermentation, the total number of moles of protons generated is always two per mole of the fermentable substrate. However, two and three times more adenosine triphosphate can be turned over per mole of protons produced in succinate and propionate fermentations, respectively, than in lactate fermentation.

NATURE OF THE HEPATOMEGALIC EFFECT PRODUCED BY ETHYL-CHLOROPHENOXY-ISOBUTYRATE IN THE RAT

1965-11-01

R. Hess , W. Stäubli , W. Rieß

Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings.

1989-08-01

Erling A. Anderson , Christine A. Sinkey , William J. Lawton +1 more

Reports of elevated plasma catecholamine levels and augmented responses to autonomic blockade suggest increased sympathetic tone in borderline hypertension. It is not known if this reflects greater sympathetic neural outflow. … Reports of elevated plasma catecholamine levels and augmented responses to autonomic blockade suggest increased sympathetic tone in borderline hypertension. It is not known if this reflects greater sympathetic neural outflow. We directly recorded muscle sympathetic nerve activity (microneurography) in 15 normotensive and 12 borderline hypertensive age-matched men to determine whether borderline hypertensive individuals have elevated sympathetic nerve activity. Supine heart rate, blood pressure, plasma norepinephrine, and efferent muscle sympathetic nerve activity (peroneal nerve) were measured after 6 days of both low and high dietary sodium intake (10 and 400 meq sodium/24 hr). Sympathetic nerve activity was elevated significantly in borderline hypertensive individuals on both low (37 +/- 1 in borderline hypertensive individuals vs. 29 +/- 1 bursts/min in normotensive individuals; p less than 0.01) and high (25 + 1 in borderline hypertensive individuals vs. 16 +/- 1 bursts/min in normotensive individuals; p less than 0.01) sodium diets. The borderline hypertensive group had higher systolic (p less than 0.01) and diastolic (p less than 0.05) blood pressures independent of sodium intake. Across both groups, high sodium intake reduced muscle sympathetic nerve activity (p less than 0.001), plasma norepinephrine (p less than 0.001), diastolic blood pressure (p less than 0.02), heart rate (p less than 0.002), and increased weight (p less than 0.005). A significant (p less than 0.05) group-by-diet interaction was observed for plasma norepinephrine levels. Specifically, compared with the normotensive group, plasma norepinephrine levels in the borderline hypertensive group tended to be higher on low sodium diet (p = 0.08) and lower on high sodium diet (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of Membrane Potential and pH Difference across the Cristae Membrane of Rat Liver Mitochondria

1969-02-01

Peter Mitchell , Jennifer Moyle

The cristae membrane or M phase of resting or respiring rat liver mitochondria becomes relatively permeable to K + ions in presence of valinomycin. The equilibrium distribution of K + … The cristae membrane or M phase of resting or respiring rat liver mitochondria becomes relatively permeable to K + ions in presence of valinomycin. The equilibrium distribution of K + ions across the membrane can therefore be used to estimate the membrane potential ΔΨ provided that precautions are taken to minimise swelling of the valinomycin‐treated mitochondria. The pH difference ΔpH across the M phase of anaerobic mitochondria has been estimated from the buffering powers of the inner and outer phases and from the change of pH observed on lysing the mitochondria with Triton X‐100. When the anaerobic mitochondria (State 5), in presence of β‐hydroxybutyrate, are brought to a state of steady respiration either in absence (State 4) or in presence (State 3) of phosphate acceptor, the changes of pH and of pK of the medium recorded with H + ion‐sensitive and K + ion‐sensitive electrodes can be used to estimate the changes of ΔΨ and ΔpH across the M phase. The absolute values of ΔΨ and ΔpH have been estimated from the values determined in State 5 and the change of these values in the transition from State 5 to States 4 and 3. The total protonmotive force Δp =ΔΨ– 59 ΔpH across the M phase of the mitochondria oxidising β‐hydroxybutyrate in State 4 at 25° in a 250 mM sucrose medium near pH 7 is estimated to be about 230 mV, of which the major component is ΔΨ when the effect of translocation of K + ions across the M phase is minimised. Under conditions permitting accumulation of a relatively large quantity of cation (State 6), Δp is not significantly different from that in State 4, but the major component is − Z ΔpH. The effects of changing Δp in mitochondrial suspensions in State 4 with uncoupling agent and with pulses of acid, alkali, calcium salt and ADP have been found to be in accord with the chemiosmotic hypothesis. In particular Δp in State 3 (ADP and Pi present) is estimated to be about 30 mV less than in State 4.

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Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue.

1975-10-01

Peter V. Hauschka , Jane B. Lian , Paul M. Gallop

A direct approach has been developed for quantitative identification of the calcium-binding amino acid, gamma-carboxyglutamate, in proteins. This should be advantageous for the study of numerous systems where specific roles … A direct approach has been developed for quantitative identification of the calcium-binding amino acid, gamma-carboxyglutamate, in proteins. This should be advantageous for the study of numerous systems where specific roles for the binding of calcium or other divalent cations are suspected. Investigation of mineralized tissue, where calcium-binding proteins are implicated in the mineralization process, revealed that gamma-carboxyglutamate was present in proteins solubilized from chicken bone with neutral aqueous ethylenediamine tetraacetic acid. This was established by direct isolation of the amino acid from alkaline hydrolysates and its quantitative conversion to glutamic acid by decarboxylation in 0.05 M HCl at 100 degrees. The kinetics of decarboxylation and chromatographic behavior are identical to those of gamma-carboxyglutamate from human prothrombin. After resolution of the soluble bone proteins by phosphate gradient elution from hydroxyapatite, gamma-carboxyglutamate was found to be concentrated primarily in one BaSO4-adsorbable anionic protein species; bone collagen was devoid of the amino acid. In view of the recently discovered requirement of vitamin K for generation of calcium binding sites (gamma-carboxyglutamate) by gamma-carboxylation of specific glutamic acid residues in prothrombin, our findings may implicate vitamin K metabolism in normal bone development and suggest a role for the gamma-carboxyglutamate-rich protein in regulation of calcium salt deposition in mineralized tissues.

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THREE "MYOSIN ADENOSINE TRIPHOSPHATASE" SYSTEMS: THE NATURE OF THEIR pH LABILITY AND SULFHYDRYL DEPENDENCE

1970-09-01

Michael H. Brooke , Kenneth K. Kaiser

Determinants of the diurnal course of salivary alpha-amylase

2007-04-06

Urs M. Nater , Nicolas Rohleder , Wolff Schlotz +2 more

Physiology and Pathophysiology of Carnosine

2013-10-01

А. А. Болдырев , Giancarlo Aldini , Wim Derave

Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most … Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.

MYELINATION IN RAT BRAIN: METHOD OF MYELIN ISOLATION1

1973-10-01

William T. Norton , Shirley E. Poduslo

Abstract— A procedure is described for the preparation from rat brain of myelin having the same degree of purity at all ages. Such a procedure is essential for the study … Abstract— A procedure is described for the preparation from rat brain of myelin having the same degree of purity at all ages. Such a procedure is essential for the study of myelin composition during development. Microsomal contamination was successfully eliminated by adjusting the method to maintain a constant amount of brain per unit volume in the initial density gradient step, and by including two osmotic shocks and two low‐speed centrifugation steps. Myelin prepared in this way from animals ranging from 15 days to 14months of age had a total ATPase activity of 0.3‐2.0 μmol of P i .h −1 .mg −1 dry wt of myelin, representing 0.1‐1.2 per cent recovery of the total homogenate activity; a Na + , K + ‐ ATPase activity of 0.1‐1.6 μfnol of P i .h −1 .mg −1 dry wt, representing 0.04‐1.5 per cent recovery; a nucleic acid content of 0.2‐0.7 per cent of myelin dry wt, representing 0.2‐2.0 per cent recovery; and a ganglioside NANA content of 0.04‐0.07 per cent of myelin dry wt. representing 0.2‐4.6 per cent recovery. The myelin prepared from 20‐day animals had the highest content of the first three constituents; otherwise the values of the four constituents were relatively constant per unit weight of myelin. The amounts of nucleic acid and ganglioside recovered in the myelin fractions increased with increasing age and myelin yield.

Acute effects of cigarette smoke on inflammation and oxidative stress: a review

2004-07-28

C. H. van der Vaart , Dirkje S. Postma , Wim Timens +1 more

Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified … Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified 123 studies investigating the acute effects of cigarette smoking on inflammation and oxidative stress in human, animal, and in vitro models. An acute smoking model is a relatively easy and sensitive method of investigating the specific effects of cigarette smoke on oxidative stress and inflammation. Acute smoke exposure can result in tissue damage, as suggested by increased products of lipid peroxidation and degradation products of extracellular matrix proteins. Acute cigarette smoke has a suppressive effect on the number of eosinophils and several inflammatory cytokines, possibly due to the anti-inflammatory effect of carbon monoxide. An acute smoking model can supplement other ways of studying the effects of smoking and is an as yet underinvestigated method for intervention studies in smoking related diseases.

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Quantitative IR spectrophotometry of peptide compounds in water (H2O) solutions. I. Spectral parameters of amino acid residue absorption bands

1990-01-01

S.Yu. Venyaminov , N. N. Kalnin

Infrared spectra of the amino acid residues in H2O solution have been obtained in the 1800-1400-cm-1 region. It has been established that amino acid residues of arginine, asparagine, glutamine, aspartic … Infrared spectra of the amino acid residues in H2O solution have been obtained in the 1800-1400-cm-1 region. It has been established that amino acid residues of arginine, asparagine, glutamine, aspartic and glutamic acids, lysine, tyrosine, histidine, and phenylalanine have intensive absorption in this spectral region. Infrared spectra for a set of model compounds have been measured. On the basis of these data, spectral parameters of amino acid residue absorption bands have been determined.

β-Amyloid Peptides Induce Mitochondrial Dysfunction and Oxidative Stress in Astrocytes and Death of Neurons through Activation of NADPH Oxidase

2004-01-14

Andrey Y. Abramov , Laura Canevari , Michael R. Duchen

β-Amyloid (βA) peptide is strongly implicated in the neurodegeneration underlying Alzheimer's disease, but the mechanisms of neurotoxicity remain controversial. This study establishes a central role for oxidative stress by the … β-Amyloid (βA) peptide is strongly implicated in the neurodegeneration underlying Alzheimer's disease, but the mechanisms of neurotoxicity remain controversial. This study establishes a central role for oxidative stress by the activation of NADPH oxidase in astrocytes as the cause of βA-induced neuronal death. βA causes a loss of mitochondrial potential in astrocytes but not in neurons. The mitochondrial response consists of Ca 2+ -dependent transient depolarizations superimposed on a slow collapse of potential. The slow response is both prevented by antioxidants and, remarkably, reversed by provision of glutamate and other mitochondrial substrates to complexes I and II. These findings suggest that the depolarization reflects oxidative damage to metabolic pathways upstream of mitochondrial respiration. Inhibition of NADPH oxidase by diphenylene iodonium or 4-hydroxy-3-methoxy-acetophenone blocks βA-induced reactive oxygen species generation, prevents the mitochondrial depolarization, prevents βA-induced glutathione depletion in both neurons and astrocytes, and protects neurons from cell death, placing the astrocyte NADPH oxidase as a primary target of βA-induced neurodegeneration.

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Oxidative Stress in Brain Ischemia

1999-01-01

Seth Love

Brain ischemia initiates a complex cascade of metabolic events, several of which involve the generation of nitrogen and oxygen free radicals. These free radicals and related reactive chemical species mediate … Brain ischemia initiates a complex cascade of metabolic events, several of which involve the generation of nitrogen and oxygen free radicals. These free radicals and related reactive chemical species mediate much of damage that occurs after transient brain ischemia, and in the penumbral region of infarcts caused by permanent ischemia. Nitric oxide, a water- and lipid-soluble free radical, is generated by the action of nitric oxide synthases. Ischemia causes a surge in nitric oxide synthase 1 (NOS 1) activity in neurons and, possibly, glia, increased NOS 3 activity in vascular endothelium, and later an increase in NOS 2 activity in a range of cells including infiltrating neutrophils and macrophages, activated microglia and astrocytes. The effects of ischemia on the activity of NOS 1, a Ca2+-dependent enzyme, are thought to be secondary to reversal of glutamate reuptake at synapses, activation of NMDA receptors, and resulting elevation of intracellular Ca2+. The up-regulation of NOS 2 activity is mediated by transcriptional inducers. In the context of brain ischemia, the activity of NOS 1 and NOS 2 is broadly deleterious, and their inhibition or inactivation is neuroprotective. However, the production of nitric oxide in blood vessels by NOS 3, which, like NOS 1, is Ca2+-dependent, causes vasodilatation and improves blood flow in the penumbral region of brain infarcts. In addition to causing the synthesis of nitric oxide, brain ischemia leads to the generation of superoxide, through the action of nitric oxide synthases, xanthine oxidase, leakage from the mitochondrial electron transport chain, and other mechanisms. Nitric oxide and superoxide are themselves highly reactive but can also combine to form a highly toxic anion, peroxynitrite. The toxicity of the free radicals and peroxynitrite results from their modification of macromolecules, especially DNA, and from the resulting induction of apoptotic and necrotic pathways. The mode of cell death that prevails probably depends on the severity and precise nature of the ischemic injury. Recent studies have emphasized the role of peroxynitrite in causing single-strand breaks in DNA, which activate the DNA repair protein poly(ADP-ribose) polymerase (PARP). This catalyzes the cleavage and thereby the consumption of NAD+, the source of energy for many vital cellular processes. Over-activation of PARP, with resulting depletion of NAD+, has been shown to make a major contribution to brain damage after transient focal ischemia in experimental animals. Neuronal accumulation of poly(ADP-ribose), the end-product of PARP activity has been demonstrated after brain ischemia in man. Several therapeutic strategies have been used to try to prevent oxidative damage and its consequences after brain ischemia in man. Although some of the drugs used in early studies were ineffective or had unacceptable side effects, other trials with antioxidant drugs have proven highly encouraging. The findings in recent animal studies are likely to lead to a range of further pharmacological strategies to limit brain injury in stroke patients.

Amyloid β-peptide (1-42)-induced Oxidative Stress and Neurotoxicity: Implications for Neurodegeneration in Alzheimer's Disease Brain. A Review

2002-01-01

D. Allan Butterfield

Oxidative stress, manifested by protein oxidation, lipid peroxidation, DNA oxidation and 3-nitrotyrosine formation, among other indices, is observed in Alzheimer's disease (AD) brain. Amyloid beta-peptide (1-42) [Abeta(1-42)] may be central … Oxidative stress, manifested by protein oxidation, lipid peroxidation, DNA oxidation and 3-nitrotyrosine formation, among other indices, is observed in Alzheimer's disease (AD) brain. Amyloid beta-peptide (1-42) [Abeta(1-42)] may be central to the pathogenesis of AD. Our laboratory and others have implicated Abeta(1-42)-induced free radical oxidative stress in the neurodegeneration observed in AD brain. This paper reviews some of these studies from our laboratory. Recently, we showed both in-vitro and in-vivo that methionine residue 35 (Met-35) of Abeta(1-42) was critical to its oxidative stress and neurotoxic properties. Because the C-terminal region of Abeta(1-42) is helical, and invoking the i + 4 rule of helices, we hypothesized that the carboxyl oxygen of lle-31, known to be within a van der Waals distance of the S atom of Met-35, would interact with the latter. This interaction could alter the susceptibility for oxidation of Met-35, i.e. free radical formation. Consistent with this hypothesis, substitution of lle-31 by the helix-breaking amino acid, proline, completely abrogated the oxidative stress and neurotoxic properties of Abeta(1-42). Removal of the Met-35 residue from the lipid bilayer by substitution of the negatively charged Asp for Gly-37 abrogated oxidative stress and neurotoxic properties of Abeta(1-42). The free radical scavenger vitamin E prevented A(beta (1-42)-induced ROS formation, protein oxidation, lipid peroxidation, and neurotoxicity in hippocampal neurons, consistent with our model for Abeta-associated free radical oxidative stress induced neurodegeneration in AD. ApoE, allele 4, is a risk factor for AD. Synaptosomes from apoE knock-out mice are more vulnerable to Abeta-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation) than are those from wild-type mice. We also studied synaptosomes from allele-specific human apoE knock-in mice. Brain membranes from human apoE4 mice have greater vulnerability to Abeta(1-42)-induced oxidative stress than brain membranes from apoE2 or E3, assessed by the same indices, consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Using immunoprecipitation of proteins from AD and control brain obtained no longer than 4h PMI, selective oxidized proteins were identified in the AD brain. Creatine kinase (CK) and beta-actin have increased carbonyl groups, an index of protein oxidation, and Glt-1, the principal glutamate transporter, has increased binding of the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE). Abeta inhibits CK and causes lipid peroxidation, leading to HNE formation. Implications of these findings relate to decreased energy utilization, altered assembly of cytoskeletal proteins, and increased excitotoxicity to neurons by glutamate, all reported for AD. Other oxidatively modified proteins have been identified in AD brain by proteomics analysis, and these oxidatively-modified proteins may be related to increased excitotoxicity (glutamine synthetase), aberrant proteasomal degradation of damaged or aggregated proteins (ubiquitin C-terminal hydrolase L-1), altered energy production (alpha-enolase), and diminished growth cone elongation and directionality (dihydropyrimindase-related protein 2). Taken together, these studies outlined above suggest that Met-35 is key to the oxidative stress and neurotoxic properties of Abeta(1-42) and may help explain the apoE allele dependence on risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Abeta(1-42)-induced oxidative stress and neurodegeneration in AD.

The spectrophotometric determination of tyrosine and tryptophan in proteins

1946-01-01

T. W. Goodwin , R. A. Morton

Research Article| January 01 1946 The spectrophotometric determination of tyrosine and tryptophan in proteins T. W. Goodwin; T. W. Goodwin 1Johnston Laboratories, Department of Biochemistry, University of Liverpool Search for … Research Article| January 01 1946 The spectrophotometric determination of tyrosine and tryptophan in proteins T. W. Goodwin; T. W. Goodwin 1Johnston Laboratories, Department of Biochemistry, University of Liverpool Search for other works by this author on: This Site PubMed Google Scholar R. A. Morton R. A. Morton 1Johnston Laboratories, Department of Biochemistry, University of Liverpool Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd © 1946 CAMBRIDGE UNIVERSITY PRESS1946 Biochem J (1946) 40 (5-6): 628–632. https://doi.org/10.1042/bj0400628 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation T. W. Goodwin, R. A. Morton; The spectrophotometric determination of tyrosine and tryptophan in proteins. Biochem J 1 January 1946; 40 (5-6): 628–632. doi: https://doi.org/10.1042/bj0400628 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1946 CAMBRIDGE UNIVERSITY PRESS1946 Article PDF first page preview Close Modal You do not currently have access to this content.

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Oxidative Stress and the Central Nervous System

2016-10-17

Samina Salim

Biochemical integrity of the brain is vital for normal functioning of the central nervous system (CNS). One of the factors contributing to cerebral biochemical impairment is a chemical process called … Biochemical integrity of the brain is vital for normal functioning of the central nervous system (CNS). One of the factors contributing to cerebral biochemical impairment is a chemical process called oxidative stress. Oxidative stress occurs upon excessive free radical production resulting from an insufficiency of the counteracting antioxidant response system. The brain, with its high oxygen consumption and lipid-rich content, is highly susceptible to oxidative stress. Therefore, oxidative stress–induced damage to the brain has a strong potential to negatively impact normal CNS functions. Although oxidative stress has historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer disease, Huntington disease, and Parkinson disease, its involvement in neuropsychiatric disorders, including anxiety disorders and depression, is beginning to be recognized. This review is a discussion of the relevance of cerebral oxidative stress to impairment of emotional and mental well-being.

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N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why

2018-05-09

Giancarlo Aldini , Alessandra Altomare , Giovanna Baron +4 more

The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant … The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant effect is due to the ability of NAC to act as a reduced glutathione (GSH) precursor; GSH is a well-known direct antioxidant and a substrate of several antioxidant enzymes. Moreover, in some conditions where a significant depletion of endogenous Cys and GSH occurs, NAC can act as a direct antioxidant for some oxidant species such as NO2 and HOX. The antioxidant activity of NAC could also be due to its effect in breaking thiolated proteins, thus releasing free thiols as well as reduced proteins, which in some cases, such as for mercaptoalbumin, have important direct antioxidant activity. As well as being involved in the antioxidant mechanism, the disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins. Chemical features explaining the efficient disulphide breaking activity of NAC are also explained.

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Structure of the porcine LH- and FSH-releasing hormone. I. The proposed amino acid sequence

1976-08-01

Hormesis defined

2007-12-06

Mark P. Mattson

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An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases

2022-05-25

Daniel Mihai Teleanu , Adelina-Gabriela Niculescu , Iulia Ioana Lungu +6 more

Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress of several neurodegenerative disorders. This review intends to summarize some of the findings … Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress of several neurodegenerative disorders. This review intends to summarize some of the findings that correlate the overproduction of reactive oxygen species with the pathophysiology of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Oxidative stress was also noted to modify the inflammatory response. Even though oxidative stress and neuroinflammation are two totally different pathological events, they are linked and affect one another. Nonetheless, there are still several mechanisms that need to be understood regarding the onset and the progress of neurodegenerative diseases in order to develop efficient therapies. As antioxidants are a means to alter oxidative stress and slow down the symptoms of these neurodegenerative diseases, the most common antioxidants, enzymatic as well as non-enzymatic, have been mentioned in this paper as therapeutic options for the discussed disorders.

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CONCISE ALGORITHM «PREMENSTRUAL SYNDROME»

2025-06-24

| Akušerstvo i ginekologiâ

Biological properties, synthetic pathways and anti-aging mechanisms of nicotinamide mononucleotide (NMN): Research progress and challenges

2025-06-23

Enhui Wang , Yuting Wang , Zhaofeng Zhang +2 more | Biogerontology

Steric Control of Copper(II) Coordination by Carnosine: Role of the β-Alanyl Methylene Spacer

2025-06-21

Feng Xue-yu , Chunyang Wang , Yangfan He +2 more | The Journal of Physical Chemistry Letters

Carnosine (β-alanyl-l-histidine), the shortest histidine-containing natural peptide in mammalian tissues, regulates crucial biological processes through Cu(II) chelation. Using a multitechnique approach combining potentiometric titration and UV-vis, EPR, FTIR, and 2D … Carnosine (β-alanyl-l-histidine), the shortest histidine-containing natural peptide in mammalian tissues, regulates crucial biological processes through Cu(II) chelation. Using a multitechnique approach combining potentiometric titration and UV-vis, EPR, FTIR, and 2D IR spectroscopy, we identified and characterized three distinct Cu(II)-carnosine complexes with pH-dependent speciation. Structural comparison with glycyl-l-histidine demonstrates that the extended methylene spacer of carnosine introduces unique steric constraints that (i) inhibits amide hydrogen substitution by Cu(II), (ii) facilitates formation of the binuclear species [Cu2LH-1]II, and (iii) promotes subsequent dimerization to [Cu2L2H-2] under acidic to neutral conditions. At alkaline pH, the protonation state of carnosine N-terminus serves as a critical regulator of Cu(II) coordination geometry, dictating metal binding affinity and determining site preference between N- and C-terminal coordination motifs.

Differential neuroprotective mechanisms of rosemary and carnosic acid in cerebral ischemia-reperfusion injury

2025-06-21

W.-B. Li , Cuiying Liu , Can Xu +4 more | Neurological Research

Rosemary is a traditional Chinese medicinal herb recognized for its therapeutic potential in cardiovascular and cerebrovascular diseases. Its primary active constituent, carnosic acid, has been shown to reduce infarct volume … Rosemary is a traditional Chinese medicinal herb recognized for its therapeutic potential in cardiovascular and cerebrovascular diseases. Its primary active constituent, carnosic acid, has been shown to reduce infarct volume in ischemic stroke models. However, the mechanisms underlying the effects of rosemary and carnosic acid, and their specific actions in ischemic stroke remain incompletely understood. In this study, we evaluated the therapeutic effects of rosemary and carnosic acid using a middle cerebral artery occlusion/reperfusion model, and predicted their mechanisms of action network pharmacology and molecular docking approaches, with key targets subsequently validated using quantitative PCR analysis. The results showed that both rosemary and carnosic acid significantly reduced infarct volume and improved neurological function. Rosemary treatment increased spleen weight, suggesting a potential immunomodulatory role, whereas carnosic acid had no significant effect on spleen weight. Network pharmacology analysis indicated that rosemary regulated multiple molecular pathways, including the VEGF, PI3K-Akt, and TNF signaling pathways, while carnosic acid primarily influenced pathways associated with apoptosis and inflammation. Molecular docking and qPCR validation further demonstrated that carnosic acid modulated apoptosis through key targets such as TNF-α, TP53, MMP9, and PPARG. Rosemary and carnosic acid exert neuroprotective effects in cerebral ischemia-reperfusion injury through distinct mechanisms, demonstrating their potential as complementary therapeutic agents for ischemic stroke.

Effects of Creatine and β-Alanine Co-Supplementation on Exercise Performance and Body Composition: A Systematic Review

2025-06-21

Damoon Ashtary‐Larky , Darren G. Candow , Scott C. Forbes +3 more | Nutrients

Background/Objectives: Creatine and β-alanine are two widely used dietary supplements known to enhance exercise performance and improve body composition; however, less is known regarding the synergistic effects of combining the … Background/Objectives: Creatine and β-alanine are two widely used dietary supplements known to enhance exercise performance and improve body composition; however, less is known regarding the synergistic effects of combining the two supplements. Methods: A systematic search was conducted across PubMed/MEDLINE, Scopus, and Web of Science databases for randomized controlled trials (RCTs) published up to March 2025. Eligible studies included adult participants receiving creatine and β-alanine together compared to creatine or β-alanine alone for at least four weeks and assessed measures of exercise performance and/or body composition. Study quality was assessed using the Cochrane Risk of Bias tool. Results: A total of 7 randomized controlled trials (n = 263 participants; 231 males and 32 females) met the inclusion criteria. Collectively, the combination of creatine and β-alanine supplementation enhanced high-intensity exercise performance, particularly anaerobic power and repeated-bout performance, compared to creatine or β-alanine alone. Co-ingestion of creatine and β-alanine supplementation did not increase measures of maximal strength compared to creatine alone. The effects of creatine and β-alanine supplementation on body composition were equivocal, with one study reporting greater lean mass gains and fat mass reductions compared to creatine and β-alanine supplementation individually, while another found no significant improvements. Additionally, no significant improvements in aerobic endurance capacity (VO2max, lactate threshold, or time to exhaustion) were observed from creatine and β-alanine supplementation co-ingestion. Conclusions: The combination of creatine and β-alanine supplementation may be effective for enhancing high-intensity exercise performance but has no greater effect on maximal strength, body composition, or measures of aerobic capacity compared to creatine or β-alanine alone.

Relationship between Advanced Glycation End-products, Serum Carnosinase-1 and Diabetic Nephropathy and Diabetic Retinopathya

2025-06-20

Yu Rong | Journal of Medical Biochemistry

Introduction: This article analyzed the relationship between serum advanced glycation end-products (AGEs), carnosinase-1 (CN-1) and diabetic nephropathy (DN) and diabetic retinopathy (DR). Material and Method: 150 patients with type 2 … Introduction: This article analyzed the relationship between serum advanced glycation end-products (AGEs), carnosinase-1 (CN-1) and diabetic nephropathy (DN) and diabetic retinopathy (DR). Material and Method: 150 patients with type 2 diabetes mellitus (DM2) were grouped: DN and non-DN, DR and non-DR groups. Fasting venous blood was collected, and serum levels of AGEs and CN-1 were detected. Pearson’s correlation (PC) test was adopted for analyzing their correlation with DN and DR, and multivariate Logistic regression (MLR) analysis was adopted. Result: There were 48 DN cases, 102 non-DN cases, 20 DR cases, and 130 non-DR cases in 150 patients with DM2. As against the non-DN group, the serum levels of AGEs and CN-1 in the subjects with DN were markedly increased. As against the non-DR group, the serum levels of AGEs and CN-1 in the subjects with DR were also markedly increased. The results of correlation analysis revealed that the levels of serum AGEs and CN-1 were positively correlated with the occurrence of DN and DR. Serum AGEs and CN-1 levels were independent risk factors (IRF) for DN and DR (all P <0.05). Conclusion: AGEs and CN-1 may become new targets for the diagnosis and remedy of diabetic microvascular complications.

Gamma-oryzanol as a potential intervention in obesity and skeletal muscle disorders: a preclinical review from rodent studies

2025-06-20

Thiago Luiz Novaga Palacio , Juliana Silva Siqueira , Camila Renata Corrêa | Nutrire

The development of chicken meat flavor from the interaction between Maillard reaction intermediates and enzymatically hydrolyzed-oxidized chicken fat

2025-06-20

Huan Zhan , Yanfang Jiang , Maosen Xu +5 more | Food Research International

Metabolomic analysis of blood spots in a Chinese cohort with autism spectrum disorders: a pilot study

2025-06-20

Hui Wang , Li Ding , Zheng-huan Mao +6 more | Metabolic Brain Disease

Effects of L-thyroxine on wound healing and secretion of cytokines in hypo- and hyperthyroid rats

2025-06-20

Александр Александрович Минченко , Artur Khasanov , Alexandra S. Buntovskaya +6 more | Reviews on Clinical Pharmacology and Drug Therapy

Aim: Assess the effects of systemic and topical L-thyroxine on the experimental wound healing. Materials and methods: 74 white nonlinear male rats weighing 220–257g, the wound healing effects of drug-induced … Aim: Assess the effects of systemic and topical L-thyroxine on the experimental wound healing. Materials and methods: 74 white nonlinear male rats weighing 220–257g, the wound healing effects of drug-induced hyper- and hypothyroidism and L-thyroxine containing hydrogel at a concentration of 10μg/ml on a grade IIIB thermal skin burn model were examined. The animals were randomized into 3 experimental and 2 comparison groups: Ia — systemic L-thyroxine-induced hyperthyroidism, Ib — local application of L-thyroxine-containing hydrogel, II — systemic propylthiouracil (PTU)-induced hypothyroidism, IIIa — positive control (Levomekol ointment), IIIb — intact control. Seventy-two hours after the burn, the wound was freed from scab by complete excision along the border of the intact skin, a splinting ring was applied, and the study drugs were administered. On the 10th day after the burn, the levels of IFN-γ, DEFa1, TGFb1, FGF2 were determined using ELISA. The area of the burn wound was assessed by the Universal Desktop Ruler program. Results: The median time of 50% epithelialization in the Ia and Ib groups was 20 and 21 days and were significantly less than the intact control. The median time to 75% wound epithelialization in all experimental groups differed significantly from both control groups: in Ia and Ib groups it was 29.5, 30.2±0.9 and 33.3±0.45 days, while the median time to 75% epithelialization in the PTU-induced hypothyroidism group was not achieved. The levels of INF-γ, DEFa1, TGFb1, FGF2 in wound discharge in the systemic hyperthyroidism group and the levels of FGF2 and INF-γ in the local hyperthyroidism group were statistically significantly increased compared to both control groups. In the PTU-induced hypothyroidism group the levels of FGF2 and INF-γ demonstrated a statistically significant decrease compared to the control groups. Conclusion. Thyroid hormones demonstrate dose-dependent effects on the secretion of FGF2 and INF-γ. Conclusions: Systemic hyperthyroidism and application of thyroxine-containing gel to the wound surface leads to acceleration of the "natural course of the wound process". Thyroid hormones exhibit dose-dependent effects on the secretion of FGF2 and INF-γ.

Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages

2025-06-19

Shuai Ma , Bin Yang , Yuyang Sun +7 more | eLife

Salmonella is a major foodborne pathogen that can effectively replicate inside host macrophages to establish life-threatening systemic infections. Salmonella must utilize diverse nutrients for growth in nutrient-poor macrophages, but which … Salmonella is a major foodborne pathogen that can effectively replicate inside host macrophages to establish life-threatening systemic infections. Salmonella must utilize diverse nutrients for growth in nutrient-poor macrophages, but which nutrients are required for intracellular Salmonella growth is largely unknown. Here, we found that either acquisition from the host or de novo synthesis of a nonprotein amino acid, β-alanine, is critical for Salmonella replication inside macrophages. The concentration of β-alanine is decreased in Salmonella -infected macrophages, while the addition of exogenous β-alanine enhances Salmonella replication in macrophages, suggesting that Salmonella can uptake host-derived β-alanine for intracellular growth. Moreover, the expression of panD, the rate-limiting gene required for β-alanine synthesis in Salmonella, is upregulated when Salmonella enters macrophages. Mutation of panD impaired Salmonella replication in macrophages and colonization in the mouse liver and spleen, indicating that de novo synthesis of β-alanine is essential for intracellular Salmonella growth and systemic infection. Additionally, we revealed that β-alanine influences Salmonella intracellular replication and in vivo virulence partially by increasing expression of the zinc transporter genes znuABC , which in turn facilitates the uptake of the essential micronutrient zinc by Salmonella . Taken together, these findings highlight the important role of β-alanine in the intracellular replication and virulence of Salmonella , and panD is a promising target for controlling systemic Salmonella infection.

Functional feed ingredients modulate the immune response of RTgutGC cells to LPS-induced inflammation

2025-06-18

M. FOSSE , Laura Rivera Méndez , Tania Rodríguez‐Ramos +3 more | Frontiers in Immunology

Functional feed ingredients can enhance the fish gut integrity and immune resilience during challenging situations in the aquaculture industry. This study used the RTgutGC cell line – derived from rainbow … Functional feed ingredients can enhance the fish gut integrity and immune resilience during challenging situations in the aquaculture industry. This study used the RTgutGC cell line – derived from rainbow trout intestinal epithelium, to evaluate the immunomodulatory and barrier effects of selected ingredients. These included β-glucan from Saccharomyces cerevisiae (BG40 and BG60), laminarin extracted from Laminaria hyperborea (Lam60 and Lam90), and bioactive peptides with antioxidative and immunomodulatory potential; carnosine (Carn100 and Carn120) and salmon hydrolysate (FPH300 and FPH600). Cells were exposed for 24 hours at two concentrations (maintaining 100 % and 80 % viability), and effects on transepithelial resistance (TEER), permeability (P app ) and gene expression (qPCR) were assessed before and after a 6-hour lipopolysaccharide (LPS) challenge. High-dose laminarin and both salmon hydrolysate concentrations elevated mRNA encoding for pro-inflammatory cytokines ( il6 , il8 , il1b and tnfa ; p &lt; 0.05). All ingredients except carnosine significantly reduced TEER ( p &lt; 0.05) often with downregulation of barrier genes. Low-dose carnosine and laminarin reduced P app of Lucifer yellow, indicating less barrier disruption. LPS induced inflammation, barrier dysfunction and reduced proliferation. These effects were modulated by high-dose β-glucan and both laminarin concentrations, which significantly reduced il6 expression ( p &lt; 0.05). High-dose salmon hydrolysate also tended to reduce il6 ( p = 0.05) and increased pcna expression ( p &lt; 0.001), suggesting tissue recovery. Low-dose laminarin and both carnosine concentrations upregulated cldn3 post-challenge ( p &lt; 0.05). These findings support the RTgutGC model as a valuable screening tool and provides new insights into the biological activity and immunomodulatory effects of various functional feed ingredients.

Molecular Mechanisms Behind Organ-Related Aging and Regulatory Effects of Natural Therapeutics

2025-06-17

Rimsha Abaidullah , Shaukat Ali , Muhammad Summer +1 more | Cell Biochemistry and Biophysics

Inhibiting H2O2-Induced Aggregation of Human γD-Crystallin with Nanoformulations of Polyphenols

2025-06-17

Sony Moni Das , Apurv Gaur , Shashank Deep | Langmuir

Cataract, one of the leading causes of vision loss, is primarily caused by the aggregation of crystallin proteins in the eye lens. This research work examines how oxidative stress, triggered … Cataract, one of the leading causes of vision loss, is primarily caused by the aggregation of crystallin proteins in the eye lens. This research work examines how oxidative stress, triggered by H2O2, influences the aggregation of human γD-crystallin. Techniques such as turbidity assay, thioflavin T (ThT) assay, circular dichroism (CD) spectroscopy, 1-anilinonapthalene-8-sulfonate (ANS) binding assay, Fourier transform infrared (FTIR) study, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, and transmission electron microscopy (TEM) confirm the aggregation of protein in the presence of H2O2-forming fibrils. Polyphenols, resveratrol and quercetin, are observed not only to inhibit protein aggregation caused by H2O2 but can be used to break the fibrils. A nanodelivery system prepared from chitosan (CS) and polylactic-co-glycolic acid (PLGA) was used to encapsulate the polyphenols. TEM, dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) were used to characterize the nanoparticles (NPs). NPs are 100 nm in size, crystalline in nature, and nontoxic to cells. They improve the bioavailability of polyphenols. Multiple approaches were used to confirm that CS-PLGA NPs loaded with quercetin and resveratrol effectively prevented γD-crystallin aggregation.

Beta-alanine supplementation improves time to exhaustion, but not aerobic capacity, in competitive middle- and long-distance runners

2025-06-17

David Marko , Ronald L. Snarr , Petr Bahenský +3 more | Journal of the International Society of Sports Nutrition

Beta-alanine (βA) is a non-essential amino acid purportedly used to enhance aerobic exercise performance. While previous research indicates the benefits of βA on time to exhaustion (TTE) and aerobic capacity … Beta-alanine (βA) is a non-essential amino acid purportedly used to enhance aerobic exercise performance. While previous research indicates the benefits of βA on time to exhaustion (TTE) and aerobic capacity (VO2peak) in adults, evidence is lacking in adolescent athletes. Thus, the purpose of this study was to determine the effects of 4 weeks of βA supplementation on aerobic performance in adolescent runners. Twenty-seven middle- and long-distance runners (aged 17.36 ± 2.17 years) were randomly divided into a βA or placebo (PL) group (maltodextrin). Subjects performed maximal graded exercise tests (GXT) and submaximal trials (SMT; 80% of VO2peak for 1500 m) on a treadmill before and after 14 and 28 days of supplementation or PL. Respiratory (VE) metabolic (VO2, RER, lactate [La]), and cardiovascular (HR) variables were measured during the GXT and SMT, along with the first (VT1) and second ventilatory threshold (VT2) and TTE monitored during the GXT only. Within- and between-group differences were assessed using a repeated-measures mixed-model analysis of variance. Findings indicated that despite a trivial increase in VO2peak over 4 weeks, the βA group increased TTE by 6.5% compared to 1.4% in the PL group (d = 0.46). Additionally, small effects in HRmax, VE, [La], and TTE were observed between groups favoring βA. Regarding the SMT, both average HR and RER decreased by 4% in the βA group, with no changes for the PL. Despite no evidence to suggest increases in VO2peak, practitioners should note that improvements in TTE may be observed after 28 days of βA supplementation in adolescent runners.

Insights into insulin signalling and oxidative stress in the Tg2576 mouse model of familial Alzheimer’s disease: effects of chronic oral galactose administration

2025-06-16

Ana Babić Perhoč , D Kovač , Jan Homolak +4 more | Journal of Neural Transmission

Preparation and characterization of a novel walnut peptide–calcium chelate and its role in promoting calcium absorption in calcium-deficient mice

2025-06-16

Yaoxin Zhang , Xuehang Wang , Yuan Qi +4 more | Journal of Agriculture and Food Research

Histidine‐Containing Dipeptides in Obesity and Cardiometabolic Health: A Systematic Scoping Review

2025-06-16

Saeede Saadati , Robel Hussen Kabthymer , Giancarlo Aldini +7 more | Obesity Reviews

ABSTRACT Background Histidine‐containing dipeptides (HCDs) have been reported to have anti‐inflammatory and antidiabetic properties. Yet, no previous reviews have examined the impact of HCDs on Type 2 diabetes (T2D) risk … ABSTRACT Background Histidine‐containing dipeptides (HCDs) have been reported to have anti‐inflammatory and antidiabetic properties. Yet, no previous reviews have examined the impact of HCDs on Type 2 diabetes (T2D) risk factors (e.g., obesity) and progression (e.g., microvascular and macrovascular complications). In this scoping review, we aimed to thoroughly examine the evidence on the effects of HCDs, particularly carnosine, which is the most studied HCD, on T2D risk factors and complications and the underlying mechanisms of action. Methods We systematically searched Ovid‐Medline, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library from inception to December 2023. We included experimental studies (animal models and cell studies), observational studies, and randomized controlled trials (RCTs) investigating the mechanism of action of HCDs and the effects of supplementation in individuals with obesity and/or T2D. Results The primary literature search yielded 10,973 articles and 121 studies were eligible for inclusion. HCDs have been shown to mitigate inflammation and improve lipid profile and glycemic control in obesity and T2D with or without microvascular and macrovascular complications. However, most studies are experimental, focusing on elucidating the potential mechanisms of action of HCDs, with limited observational data or RCTs of individuals with obesity and/or T2D. No RCTs have investigated the effects of HCDs in individuals with neuropathy, retinopathy, cerebrovascular disease, and cardiovascular disease within a diabetic context. Conclusions Although the existing evidence, predominantly from preclinical studies, generally supports the use of HCDs for improving cardiometabolic health, further human studies, especially RCTs with adequately powered sample sizes, are needed.

Neuroprotective effect of Ac-SDKP peptide in SH-SY5Y cells and rat model of Parkinson's disease against 6-OHDA-induced oxidative stress and ER stress

2025-06-16

Maryam Kamarehei , Hamid Zahednasab | Neuropeptides

Changes in the concentration of melatonin and endogenous proteins regulating carbohydrate and lipid metabolism in rats under conditions of light desynchronosis with pharmacological correction by peptide extracts from the pineal gland and pituitary gland of the reindeer (Rangifer tarandus)

2025-06-16

A. V. Sharabanov , Е. Г. Батоцыренова , Tatiana Yu. Kretser +5 more | Research and Practical Medicine Journal

Purpose of the study. To study the effect of sequential release of peptide extracts (PEE) from the pineal gland and pituitary gland of reindeer (Rangifer tarandus) on endogenous regulatory proteins … Purpose of the study. To study the effect of sequential release of peptide extracts (PEE) from the pineal gland and pituitary gland of reindeer (Rangifer tarandus) on endogenous regulatory proteins (hypoxia-inducible factor 1 alpha (HIF1α), peroxisome proliferatoractivated receptor gamma (PPARγ), soluble phosphoenolpyruvate carboxykinase 1 (PEPCK) and melatonin in the blood serum of male rats under conditions of experimental light desynchronosis. Materials and methods. Modeling of light desynchronization was carried out on two-month laboratory white outbred male rats weighing 180 ± 20 g in the number of 144 individuals. The animals were divided by the method of randomization into three main groups: 1st group represented the control, in which the normal lighting regimen was modeled (LED lighting 500 lux day/night 12/12); the 2nd group was kept in the regimen of constant illumination; the third group was kept in a regimen of constant darkness. The formation of light desynchronization was carried out for 30 days. During the first 14 days of the formation of light desynchronosis, the rats were intranasally being administered with the test substances. After 30 days from the beginning of the experiment, the rats were euthanized for the collection of biological material. The blood serum HIF1α, PPARγ, PCK1 and melatonin levels of laboratory animals were analyzed by the enzyme immunoassay method (EIA). Results. The use of PEE in two doses during light deprivation has reduced the concentration of HIF1α in the blood serum, indicating improved oxygen utilization in the tissues of experimental animals. PEE in two doses has caused a sharp increase in the concentration of the transcription factor in blood serum PPARγ, which promotes the initiation of processes regulating the exchange of lipids and carbohydrates in adipose tissue. The application of peptide extracts in two doses has revealed a decrease in the activity of PCK1 under constant illumination. With constant exposure to PEE in doses 100 mg/kg, it promotes an increase in the concentration of melatonin in the blood serum, approximately equal to the level of the control group. Conclusion. The study revealed the chronobiotic effects of PEE on the concentration of regulatory proteins and melatonin in the blood serum of male rats in the conditions of light desynchronization. It should also be noted that these effects differ from the known effects of the delta-sleep inducing peptide, which may be due to a different mechanism of molecular action.

Genistein and Vanadate Differentially Modulate Cortical GABAA Receptor/ATPase Activity and Behavior in Rats via a Phenol-Sensitive Mechanism

2025-06-15

С. А. Мензиков , Danila M. Zaichenko , Aleksey A. Moskovtsev +2 more | International Journal of Molecular Sciences

Although some GABAA receptor subtypes are involved in both the passive permeability of anions and the ATP-dependent recovery of neuronal anion concentrations, the molecular mechanisms that ensure the coordination of … Although some GABAA receptor subtypes are involved in both the passive permeability of anions and the ATP-dependent recovery of neuronal anion concentrations, the molecular mechanisms that ensure the coordination of passive and active transport processes remain unclear. Here we used fluorescence measurements to investigate the role of genistein (tyrosine kinase inhibitor) and vanadate (tyrosine phosphatase and ATPase inhibitor) in modulating GABAAR-mediated [Cl-]i/[HCO3-]i changes and ATPase activity in rat cortical neurons and HEK 293FT cells expressing the heteropentameric α2β3γ2 GABAAR isoform. We found that genistein plays an important role in the inhibition of passive GABAAR-mediated Cl- influx and Cl-ATPase activity, whereas vanadate plays an important role in the inhibition of Cl-, HCO3-ATPase activity and ATP-dependent recovery of [HCO3-]i via changes in the formation of the phosphorylated intermediate. The effect of blockers was significantly restored in the presence of phenol. In behavioral experiments, the administration of phenol has been established to induce tremors and head twitching in rats, with the involvement of GABAAR/ATPase in these behavioral responses. Genistein can reduce the adverse effects of phenol, thereby confirming the interaction of these chemicals when binding to binding receptor sites. While our data demonstrate the opposing roles of genistein and vanadate in modulating GABAAR/ATPase function in a bicarbonate-dependent manner. Such multidirectional systems are considered to be bistable elements involved in the regulatory mechanisms of synaptic plasticity.

Effects of Rumen-Protected Methionine on Meat Quality, Fatty Acid Composition, Volatile Flavor Compounds and Transcriptomics of Longissimus lumborum of Yak (Bos grunniens)

2025-06-15

Xia Wu , Zizhen Zuo , Jiajia Li +6 more | Foods

Yak (Bos grunniens) meat is popular with a unique flavor and high nutritional value. This study investigated the effects of dietary supplementation with rumen-protected methionine (RPM) on meat quality, fatty … Yak (Bos grunniens) meat is popular with a unique flavor and high nutritional value. This study investigated the effects of dietary supplementation with rumen-protected methionine (RPM) on meat quality, fatty acid composition, volatile flavor compounds, and transcriptomics of Longissimus lumborum of yak. Twenty-four male Maiwa yaks were selected and assigned to four groups: basal diet (CON), or supplementation of 5 g/d (RPM5), 10 g/d (RPM10), and 15 g/d (RPM15) RPM. The dose-dependent effects of RPM levels were evaluated through linear or quadratic trend analysis. The results showed that diet supplementation with RPM increased the intramuscular fat contents, improved composition of volatile flavor compounds and the ratio of monounsaturated fatty acids to saturated fatty acids. Compared to the CON group, there were 36, 84 and 23 up-regulated genes, and 85, 94 and 70 down-regulated genes in the RPM5, RPM10 and RPM15 groups, respectively. Gene ontology enrichment analysis revealed significant differentially expressed genes enrichment in biological processes, cellular components, and molecular functions across RPM5, RPM10, and RPM15 groups compared to the CON. KEGG pathway analysis revealed 99, 169, and 104 enriched pathways in RPM5, RPM10, and RPM15 groups, respectively. In summary, the addition of RPM to diets may provide new ideas and methods to improve meat quality of yaks.

ROS-Specific Neutralization of Bioactive Compounds: An Optical Approach

2025-06-13

Tomás J. Buenfil-Chi , Hilda Mercado-Uribe , Francisco J. Sierra-Valdez | ACS Omega

1548-P: Carnosine-Mediated Amelioration of Inflammation in Type 2 Diabetes

2025-06-13

J.N. Awoke , Sergio L. Colombo , Craig Sale +1 more | Diabetes

Introduction and Objective: The critical role of innate immune activation leading to inflammatory events in the body has become of much interest and investigation in recent times because of its … Introduction and Objective: The critical role of innate immune activation leading to inflammatory events in the body has become of much interest and investigation in recent times because of its strategic importance in diabetes pathophysiology. Therefore, therapeutic targeting of innate immune activation may provide a new approach to treatment/management of diabetes. Carnosine is a physiological dipeptide consisting of β-alanine and L-histidine with emerging anti-diabetic potential. We investigated anti-inflammatory actions of carnosine in mitigating macrophage activation and glucolipotoxicity-mediated inflammation in pancreatic β-cells. Methods: Macrophages derived from human monocytes were exposed to LPS/IFNγ media supplemented with or without carnosine for 24 hrs. Cytokines were quantified in the cell supernatants using Bio-Plex Pro Human17-plex Assay. Cellular oxidative level was also measured. Additionally, pancreatic β-cells were exposed to glucolipotoxic (GLT) levels of glucose, palmitic and oleic acids supplemented with or without carnosine for 5 days. Expression level of key proteins in macrophage activation pathways and pro-inflammatory regulation in pancreatic β-cells were also investigated. Results: Carnosine suppressed both LPS/IFNy-mediated macrophage activation and GLT-induced inflammation in β-cells with evident decrease in nuclear localization of NF-κΒ. In addition, carnosine blocked TNFR5/CD40 signaling pathways to mitigate inflammation in β-cells. Also, COX-2, STAT1 and TLR2 protein expression levels were all reduced by carnosine, with subsequent decrease in cellular oxidative stress. Importantly, carnosine significantly reduced the levels of pro-inflammatory cytokines (G-CSF, GM-CSF, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-7, TNF-α, IL-17A, IL-12 and MCP-1) released from activated macrophages. Conclusion: This data provides evidence of strong anti-inflammatory potential of carnosine, which could be beneficial in the treatment/management of diabetes. Disclosure J.N. Awoke: None. S. Colombo: None. C. Sale: Research Support; Natural Alternatives International. M.D. Turner: None. Funding Commonwealth Scholarship Commission in the UK

Effects of Phenosanic Acid in Rat Seizure Models

2025-06-13

В. А. Аниол , Н. А. Лазарева , Yulia V. Moiseeva +5 more | International Journal of Molecular Sciences

Oxidative stress and membrane damage are believed to be principally involved in the pathogenesis of epilepsy. This study aimed to assess the effects of phenosanic acid (PA), an antioxidant and … Oxidative stress and membrane damage are believed to be principally involved in the pathogenesis of epilepsy. This study aimed to assess the effects of phenosanic acid (PA), an antioxidant and membrane protector, in acute pentylenetetrazole and chronic lithium–pilocarpine seizure models in male Wistar rats. PA was administered acutely (ip, 120 mg/kg BW ip, or 240 mg/kg BW per os) or chronically (80 mg/kg BW/day per os). Indices of free radical oxidation, the hypothalamo–pituitary–adrenocortical axis, and the nitrergic system were assessed in blood and brain regions. Morphological analysis of the hippocampus was performed in the lithium–pilocarpine model. PA exerted an acute anti-seizure effect in the pentylenetetrazole model. In the lithium–pilocarpine model, acute PA treatment decreased the death rate and corticosterone levels in the neocortex and brainstem. In contrast, the level of free radical oxidation products reacting with thiobarbituric acid declined in the brain stem in response to chronic PA treatment. In the lithium–pilocarpine model, the neuronal density in the dentate gyrus was elevated, and the proliferating cell nuclear antigen positive (PCNA+) cell counts in the subgranular zone did not differ between groups. Doublecortin positive (DCX+) cell count was significantly increased after chronic PA treatment. PA-induced reduction in mortality in the lithium–pilocarpine epilepsy model may be partially mediated by decreasing the lipid peroxidation and corticosterone levels in different brain regions. Chronic PA treatment may affect adult hippocampal neurogenesis by either prolonging the action of factors that increase neurogenesis after status epilepticus or by slowing down the neuronal differentiation rate. These data suggest that PA may be a disease-modifying AED able to hamper epileptogenesis.

Biochemical and Total Antioxidant Effects of Iron Oxide Nanoparticles on Liver Mice

2025-06-12

Osamah Abdullah El-Rubaidi , Dhyiaa A. Jasim , Qusay S Atwan +2 more | Asian Journal of Dairy and Food Research

Background: This study focused on Iron oxide nanoparticles (Fe2O3-NPs) from multiple concentrations of Iron oxide nanoparticles (Fe2O3-NPs) on oxidation of lipids, the defence system of antioxidants and biochemical measurements in … Background: This study focused on Iron oxide nanoparticles (Fe2O3-NPs) from multiple concentrations of Iron oxide nanoparticles (Fe2O3-NPs) on oxidation of lipids, the defence system of antioxidants and biochemical measurements in the liver of male mice. Methods: Twenty male Albino Mice weighing 25-30 g were used in the study. Animals were categorised into four groups, each comprising 10 mice. The initial group served as the control. Groups II, III and IV received oral administration of Tin oxide nanoparticles at 50, 25 and 10 mg/kg weight body per day for four weeks. Blood and liver samples were collected after the experimental period to investigate various parameters. Result: Treatment with Iron oxide nanoparticles (Fe2O3-NPsin) varying concentrations elevated levels of in comparison to the control group, the liver and kidneys exhibited reduced glutathione (GSH) content, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities, as well as hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS). The protein contents of rats were significantly reduced when they were administered iron oxide nanoparticles (Fe2O3-NPs) at concentrations that differed from those of the control group. Treatment with iron oxide nanoparticles (Fe2O3-NPs) at varying concentrations substantially increased urea and creatinine. In mice, an increase in urea and creatinine concentration is a substantial indicator of liver dysfunction. In mouse liver homogenates, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly reduced when treated with iron oxide nanoparticles (Fe2O3-NPs) at varying concentrations. Conversely, lactate dehydrogenase (LDH) was significantly increased. It is clear that iron oxide nanoparticles (Fe2O3-NPs) induce pronounced hazardous effects in the liver of mice in a dose-dependent manner, Biomarkers for the detrimental effects of iron oxide nanoparticles (Fe2O3-NPs) may include estimating lipid peroxidation, enzymatic and non-enzymatic antioxidants and biochemical parameters.

Resistance of HEK-293 and COS-7 cell lines to oxidative stress as a model of metabolic response

2025-06-12

Monika Sapeta-Nowińska , Katarzyna Sołtys , Katarzyna Gębczak +2 more | Acta Biochimica Polonica

Oxidative stress (OS), arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cellular dysfunction and the pathogenesis of numerous diseases. This … Oxidative stress (OS), arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cellular dysfunction and the pathogenesis of numerous diseases. This study evaluates the impact of oxidative stress induced by hydrogen peroxide on the metabolomic profiles of the human embryonic kidney (HEK-293) and African green monkey kidney (COS-7) cell lines. Viability (MTT) and free radical accumulation (DCF-DA) assays confirmed a dose-dependent cytotoxic effect of hydrogen peroxide, with COS-7 cells exhibiting greater resistance and producing lower levels of intracellular ROS compared to HEK-293. Metabolomic profiling was conducted using nuclear magnetic resonance spectroscopy ( 1 H NMR) to identify and quantify metabolic changes. Exposure to a free radical inducer significantly altered both intracellular and extracellular metabolites compared to control H 2 O 2 -free samples. The analysis revealed common changes in intracellular metabolites between the two lines, including glutamate, NAD + , glutathione, ATP/ADP, AMP, and pyruvate — key molecule for mitochondrial function, as well as extracellular metabolites such as glutamate, glutamine, acetate, lactate, and pyruvate. Metabolomic differences observed in COS-7 cells suggest a potentially greater capacity for metabolic adaptation to oxidative stress. These included elevated levels of branched-chain amino acids (BCAA), supporting energy production, and increased formate production, which may aid purine synthesis and cellular resilience. These findings highlight the distinct metabolic adaptations of COS-7 cells to oxidative stress in comparison to the HEK-293 cell line. They also provide insights into the direct cellular responses to altered redox potential, offering possible therapeutic strategies aimed at targeting metabolic pathways to mitigate oxidative stress.

Cherry Juice Improves Memory and Anxiety by Modulating Cell Number in the Hippocampus of Male Rat Pups Infected with Lipopolysaccharides During Gestation and Gestation-Lactation

2025-06-12

Juan Jesús Vírgen Gen , Mayvi Alvarado , Rosa Isela Guzmán-Gerónimo +3 more | International Journal of Molecular Sciences

Exposure to lipopolysaccharides (LPS) during pregnancy have been linked to alterations in the offspring’s central nervous system. Cherries are a source of anthocyanins, which possess neuroprotective properties. The study aimed … Exposure to lipopolysaccharides (LPS) during pregnancy have been linked to alterations in the offspring’s central nervous system. Cherries are a source of anthocyanins, which possess neuroprotective properties. The study aimed to evaluate the neuroprotective effects of cherry juice (CJ) on memory and hippocampal cell counts in offspring exposed to LPS during gestation and the gestation-lactation periods. At postnatal day 90, rat pups were divided into five groups: Control (saline solution), LPS-G (LPS during gestation), LPS-G+CJ (LPS during gestation+CJ), LPS-GL (LPS during gestation-lactation), and LPS-GL+CJ (LPS during gestation-lactation+CJ). A battery of behavioral tests was conducted to assess short- and long-term memory and anxiety-like behavior. Histological analysis was performed on hippocampal regions. Leukocyte levels were measured as markers of systemic inflammation. Results showed that pups in the LPS-G and LPS-GL groups exhibited impaired memory, increased anxiety-like behavior, elevated leukocyte levels, and reduced cell counts in the dentate gyrus and CA1 regions, as well as in CA2 (LPS-G) and CA3 (LPS-GL). Cherry juice administration in the LPS-G+CJ and LPS-GL+CJ groups improved memory performance, normalized leukocyte levels, and restored hippocampal cell counts. These findings suggest that cherry juice exerts neuroprotective effects against LPS-induced neuroinflammation during gestation and the gestation-lactation periods.

The Effects of the Association Between a High-Fat Diet and Physical Exercise on BDNF Expression in the Hippocampus: A Comprehensive Review

2025-06-12

Francisca Tayná da Silva Gomes , Antônio Vicente Dias de Andrade , Paloma Katlheen Moura Melo +7 more | Life

High-fat diets, characterised by their high lipid content, have been associated with structural and functional alterations in the hippocampus of rodents, including a reduction in the expression of brain-derived neurotrophic … High-fat diets, characterised by their high lipid content, have been associated with structural and functional alterations in the hippocampus of rodents, including a reduction in the expression of brain-derived neurotrophic factor (BDNF), which negatively impacts learning and memory. Evidence suggests that these impairments may be attenuated by regular physical exercise. This review aimed to gather relevant scientific evidence available on the effects of the association between high-fat diets and physical exercise on BDNF expression levels in the hippocampus of rats. The studies analysed highlight a neuroprotective effect of exercise, capable of positively modulating BDNF levels and, consequently, improving the cognitive functions of these animals.

Neurotoxicity study of copper oxide nanoparticles and the protective role of a probiotic ( Lactobacillus acidophilus ) in Swiss albino mice

2025-06-10

Manisha Sharma , Neelu Kanwar Rajawat | Toxicology and Industrial Health

Nanoparticles (NPs 1–100 nm) play a vital role in medicine, food, and agriculture owing to their unique reactivity and size-dependent optical properties. There are growing concerns about health risks from … Nanoparticles (NPs 1–100 nm) play a vital role in medicine, food, and agriculture owing to their unique reactivity and size-dependent optical properties. There are growing concerns about health risks from exposure to engineered NPs. Among these, copper oxide nanoparticles (CuONPs) are an area of research because of their unique electronic, optical, and chemical properties. CuONPs can interact with biological systems, causing oxidative stress, inflammation, neurobehavioral changes, and other pathophysiological effects. This study evaluated the ability of a probiotic ( Lactobacillus acidophilus ) to prevent CuONP-treated neurotoxicity. In the present study, 24 animals were classified into four groups: control, probiotic ( Lactobacillus acidophilus 6.42 mg/kg b.wt.), CuONPs-treated (80 mg/kg b.wt.), and co-administered CuONPs (80 mg/kg b.wt.) + Probiotic (6.42 mg/kg b.wt.). Neurotoxicity was assessed through behavioral tests, including open field, exploratory behavior, pole test, and grip strength tests. Levels of key neurotransmitters viz. acetylcholinesterase, dopamine, and serotonin were measured and histopathological analyses were performed. The CuONP-treated group displayed significant behavioral deficits, decreased neurotransmitter levels, and histopathological abnormalities. In contrast, co-administration of probiotic with CuONPs reduced these effects, as observed by normal behavioral parameters and neurotransmitter levels and improved histopathological architecture. These findings suggested that CuONPs caused neurotoxicity at the tested dose, but co-administration of probiotic effectively mitigated this toxicity. Hence, a probiotic is a promising preventative strategy against CuONP-induced neurotoxic effects.

Beta‐Alanine Relieves Symptoms in Primary Orthostatic Tremor

2025-06-09

Karolina af Edholm | Movement Disorders

Glycated walnut peptide-calcium chelates: Structural properties, calcium absorption enhancement mechanism, and osteogenic effects

2025-06-03

Zilin Wang , Haifen Jiang , Jiahe Dai +5 more | Food Chemistry

Glycosidic and peptidyl bond cleavage reactions of maltosylated carnosine

2025-06-03

Xue Xia , Varoujan A. Yaylayan | Food Chemistry