Carnosine Abstracts

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The following is a list of Carnosine Abstracts from published scientific research and papers.

L-Carnosine is available in capsule form from www.integratedhealth.com.

(REFERENCE 1 OF 32)

Ann N Y Acad Sci 1998 Nov 20;854:37-53

Pluripotent protective effects of carnosine, a naturally occurring dipeptide.

Hipkiss AR, Preston JE, Himsworth DT, Worthington VC, Keown M, Michaelis J, Lawrence J, Mateen A, Allende L, Eagles PA, Abbott NJ

Molecular Biology and Biophysics Group, King’s College London, Strand, United Kingdom. alan.hipkiss@kcl.ac.uk

Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts. Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules. Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer’s disease.

 

(REFERENCE 2 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):751-6

Problems and perspectives in studying the biological role of carnosine

Boldyrev AA

International Center for Biotechnology, Department of Biochemistry, Lomonosov Moscow State University, Moscow, 119899, Russia. aab@genebee.msu.su.

In describing carnosine among the constituents of muscle tissue in 1900, V. Gulevitsch opened the question of its real biological role. Investigation of carnosine-related phenomena occurred simultaneously with the study of its metabolic transformation within the cell. It has now been demonstrated that carnosine has the ability to protect cells against oxidative stress as well as to increase their resistance toward functional exhaustion and accumulation of senile features. Mechanisms of such protection are explained in terms of proton buffering, heavy metal chelating, as well as free radical and active sugar molecule scavenging, preventing modification of biomacromolecules and keeping their native functional activity under oxidative stress. Several carnosine derivatives are characterized by different rates of splitting by tissue carnosinase and by different biological efficiencies, thus the biological significance of enzymatic modification of carnosine during its tissue metabolism may be increased resistance of cells operating under unfavorable conditions.

 

(REFERENCE 3 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):771-8

Carnosine and protein carbonyl groups: A possible relationship.

Hipkiss AR

Division of Biomolecular Sciences, GKT School of Biomedical Sciences, King’s College London, London, SE1 1UL, UK.

Carnosine has been shown to react with low-molecular-weight aldehydes and ketones and has been proposed as a naturally occurring anti-glycating agent. It is suggested here that carnosine can also react with (“carnosinylate”) proteins bearing carbonyl groups, and evidence supporting this idea is presented. Accumulation of protein carbonyl groups is associated with cellular aging resulting from the effects of reactive oxygen species, reducing sugars, and other reactive aldehydes and ketones. Carnosine has been shown to delay senescence and promote formation of a more juvenile phenotype in cultured human fibroblasts. It is speculated that carnosine may intracellularly suppress the deleterious effects of protein carbonyls by reacting with them to form protein-carbonyl-carnosine adducts, i.e., “carnosinylated” proteins. Various fates of the carnosinylated proteins are discussed including formation of inert lipofuscin and proteolysis via proteosome and RAGE activities. It is proposed that the anti-aging and rejuvenating effects of carnosine are more readily explainable by its ability to react with protein carbonyls than its well-documented antioxidant activity.

 

(REFERENCE 4 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):869-71

Use of carnosine as a natural anti-senescence drug for human beings.

Wang AM, Ma C, Xie ZH, Shen F

Department of Biochemistry, Harbin Medical University, Harbin, 150086, PR China. Wangam@ems.hrbmu.edu.cn.

Carnosine is an endogenous free-radical scavenger. The latest research has indicated that apart from the function of protecting cells from oxidation-induced stress damage, carnosine appears to be able to extend the lifespan of cultured cells, rejuvenate senescent cells, inhibit the toxicity of amyloid peptide (Abeta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of proteins and protein-DNA and protein-protein cross-linking, and maintain cellular homeostasis. Also, carnosine seems to delay the impairment of eyesight with aging, effectively preventing and treating senile cataract and other age-related diseases. Therefore, carnosine may be applied to human being as a drug against aging.

 

(REFERENCE 5 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):866-8

Carnosine as a potential anti-senescence drug.

Gallant S, Semyonova M, Yuneva M

Zoetic Neurosciences Ltd., Leighton Buzzard, Beds, LU7 7NW, Great Britain. steven.gallant@dial.pipex.com.

The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) has been found to exert an anti-senescence effect when used as a dietary supplement. Carnosine clearly improved the external appearance of experimental animals and provided beneficial physiological effects, thus maintaining the animals in better condition than control animals receiving no carnosine or a mixture of beta-alanine and L-histidine.

 

(REFERENCE 6 OF 32)

Biosci Rep 1999 Dec;19(6):581-7

Carnosine, the protective, anti-aging peptide.

Boldyrev AA, Gallant SC, Sukhich GT

Center for Molecular Medicine, Department of Biochemistry, Biological Faculty, MV Lomonosov, Moscow State University, Vorobjovy Gory, Russia. aab@1.biocenter.bio.msu.ru

Carnosine attenuates the development of senile features when used as a supplement to a standard diet of senescence accelerated mice (SAM). Its effect is apparent on physical and behavioral parameters and on average life span. Carnosine has a similar effect on mice of the control strain, but this is less pronounced due to the non-accelerated character of their senescence processes.

 

(REFERENCE 7 OF 32)

Int J Biochem Cell Biol 1998 Aug;30(8):863-8

Carnosine, a protective, anti-aging peptide?

Hipkiss AR

Molecular Biology and Biophysics Group, King’s College London, Strand, UK.

Carnosine (beta-alanyl-L-histidine) has protective functions additional to anti-oxidant and free-radical scavenging roles. It extends cultured human fibroblast life-span, kills transformed cells, protects cells against aldehydes and an amyloid peptide fragment and inhibits, in vitro, protein glycation (formation of cross-links, carbonyl groups and AGEs) and DNA/protein cross-linking. Carnosine is an aldehyde scavenger, a likely lipofuscin (age pigment) precursor and possible modulator of diabetic complications, atherosclerosis and Alzheimer’s disease.

 

(REFERENCE 8 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):843-8

A role for carnosine in cellular maintenance

Holliday R, McFarland GA

CSIRO Division of Molecular Science, Sydney, N. S. W. 1670, Australia. gail.mcfarland@molsci.csiro.au.

The dipeptide L-carnosine has beneficial effects on cultured human fibroblasts. Physiological concentrations in standard media prolong their in-vitro lifespan and strongly reduce the normal features of senescence. Late passage cells in normal medium are rejuvenated when transferred to medium containing carnosine, and become senescent when carnosine is removed. In the absence of pyruvate, carnosine is cytotoxic to neoplastic and transformed human and rodent cells. None of these effects are seen with its optical isomer, D-carnosine.

 

(REFERENCE 9 OF 32)

Biochem Biophys Res Commun (1996 Jun 14) 223(2):278-82

Carnosine sustains the retention of cell morphology in continuous fibroblast culture subjected to nutritional insult.

Kantha SS Wada S Tanaka H Takeuchi M Watabe S Ochi H

Japan Institute for Control of Aging Fukuroi City Japan.

L- Carnosine (beta-alanyl L-histidine), occurring abundantly in skeletal muscles, has been suggested to possess antioxidant and anti- aging properties. Using three different experimental approaches (microscopic, flow cytometric and ELISA for one of the markers of DNA oxidative damage) this study on rat embryonic fibroblasts demonstrates that L-carnosine at 30 mM concentration sustains the retention of cell morphology even during a nutritional insult for five weeks. Also, L-carnosine significantly reduces the formation of 8-hydroxy deoxyguanosine (8-OH dG) in the cells after four weeks of continuous culture. Thus it could be inferred that the anti-senescent effect of L-carnosine is probably linked to its inhibition of formation of intracellular 8-OH dG during oxidative stress.

 

(REFERENCE 10 OF 32)

Exp Gerontol 1999 Jan;34(1):35-45

Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts.

McFarland GA, Holliday R

CSIRO Division of Molecular Science, Sydney Laboratory, North Ryde, Australia.

We have confirmed and extended previous results on the beneficial effects of L-carnosine on growth, morphology, and longevity of cultured human fibroblasts, strains MRC-5 and HFF-1. We have shown that late-passage HFF-1 cells retain a juvenile appearance in medium containing 50 mM carnosine, and revert to a senescent phenotype when carnosine is removed. Switching cells between medium with and without carnosine also switches their phenotype from senescent to juvenile, and the reverse. The exact calculation of fibroblast lifespans in population doublings (PDs) depends on the proportion of inoculated cells that attach to their substrate and the final yield of cells in each subculture. We have shown that carnosine does not affect cell attachment, but does increase longevity in PDs. However, the plating efficiency of MRC-5 cells seeded at low density is strongly increased in young and senescent cells by carnosine, as shown by the growth of individual colonies. We have also demonstrated that very late-passage MRC-5 cells (with weekly change of medium without subculture) remain attached to their substrate much longer in medium containing carnosine in comparison to control cultures, and also retain a much more normal phenotype. Carnosine is a naturally occurring dipeptide present at high concentration in a range of human tissues. We suggest it has an important role in cellular homeostasis and maintenance.

 

(REFERENCE 11 OF 32)

Cell Mol Life Sci 2000 May;57(5):747-53

A possible new role for the anti-aging peptide carnosine.

Hipkiss AR, Brownson C

Biomolecular Sciences Division, GKT School of Biomedical Sciences, King’s College London, UK. alan.hipkiss@kcl.ac.uk

The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in surprisingly large amounts in long-lived tissues and can delay aging in cultured human fibroblasts. Carnosine has been regarded largely as an anti-oxidant and free radical scavenger. More recently, an anti-glycating potential has been discovered whereby carnosine can react with low-molecular-weight compounds that bear carbonyl groups (aldehydes and ketones). Carbonyl groups, arising mostly from the attack of reactive oxygen species and low-molecular-weight aldehydes and ketones, accumulate on proteins during aging. Here we propose, with supporting evidence, that carnosine can react with protein carbonyl groups to produce protein-carbonyl-carnosine adducts (‘carnosinylated’ proteins). The various possible cellular fates of the carnosinylated proteins are discussed. These proposals may help explain anti-aging actions of carnosine and its presence in non-mitotic cells of long-lived mammals.

 

(REFERENCE 12 OF 33)

Biochim Biophys Acta 2000 Dec 15;1524(2-3):162-170

Enhanced oxidative damage by the familial amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutants.

Kang JH, Eum WS

Department of Genetic Engineering, Division of Natural Sciences, Chongju University, 360-764, Chongju, South Korea

Some cases of familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons, is associated with mutation in the Cu,Zn-superoxide dismutase (SOD) gene SOD1. The purified FALS mutant and wild-type Cu,Zn-SODs expressed in Escherichia coli cells have identical dismutation activity whereas the hydroxyl radical formation of FALS mutants was enhanced relative to that of the wild-type enzyme. These higher free radical-generating activities of mutants facilitated the release of copper ions from their own molecules. The reaction of the mutants with hydrogen peroxide enhanced DNA strand breaks and lipid peroxidation. The results suggested that the enhanced oxidative damage of macromolecules is mediated in the Cu,Zn-SOD mutants and hydrogen peroxide system via the generation of hydroxyl radicals by a combination of the higher free radical-generating activities of mutants and a Fenton-like reaction of copper ions released from oxidatively damaged Cu,Zn-SODs. Carnosine has been proposed to act as antioxidant in vivo. We investigated whether carnosine could protect the oxidative damage induced by FALS mutants. Carnosine effectively inhibited the DNA cleavage and lipid peroxidation. These results suggest that the higher free radical-generating function of FALS mutants can lead to increased oxidative damage of macromolecules which further implicates free radical-mediated motor neuronal injury in the pathogenesis of FALS and carnosine may be explored as potential therapeutic agents for FALS patients.

 

(REFERENCE 13 OF 32)

Zh Nevrol Psikhiatr Im S S Korsakova 2000;100(10):34-8

[No title available].[Article in Russian]

The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in-patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

 

(REFERENCE 14 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):849-55

Anti-ischemic activity of carnosine

Stvolinsky SL, Dobrota

Laboratory of Clinical Neurochemistry, Institute of Neurology, Russian Academy of Medical Sciences, Moscow, 123367, Russia. sls@bio. inevro.msk.ru.

This review summarizes the data on anti-ischemic activity of carnosine. The pronounced anti-ischemic effects of carnosine in the brain and heart are due to the combination of antioxidant and membrane-protecting activity, proton buffering capacity, formation of complexes with transition metals, and regulation of macrophage function. In experimental cerebral ischemia, carnosine decreases mortality and is beneficial for neurological conditions of the animals. In cardiac ischemia, carnosine protects cardiomyocytes from damage and improves contractility of the heart. The data indicate that carnosine can be used as an anti-ischemic drug.

 

(REFERENCE 15 OF 32)

Free Radic Res Commun (1991) 12-13 Pt 1:179-85

The SOD like activity of copper:carnosine, copper:anserine and copper:homocarnosine complexes.

Kohen R Misgav R Ginsburg I

Department of Pharmacy Hebrew University of Jerusalem Hadasaah Medical Center Israel.

Carnosine, anserine and homocarnosine are natural compounds which are present in high concentrations (2-20 mM) in skeletal muscles and brain of many vertebrates. We have demonstrated in a previous work that these compounds can act as antioxidants, a result of their ability to scavenge peroxyl radicals, singlet oxygen and hydroxyl radicals. Carnosine and its analogues have been shown to be efficient chelating agents for copper and other transition metals. Since human skeletal muscle contains one-third of the total copper in the body (20-47 mmol/kg) and the concentration of carnosine in this tissue is relatively high, the complex of carnosine:copper may be of biological importance. We have studied the ability of the copper:carnosine (and other carnosine derivatives) complexes to act as superoxide dismutase. The results indicate that the complex of copper:carnosine can dismute superoxide radicals released by neutrophils treated with PMA in an analogous mechanism to other amino acids and copper complexes. Copper:anserine failed to dismute superoxide radicals and copper:homocarnosine complex was efficient when the cells were treated with PMA or with histone-opsonized streptococci and cytochalasine B. The possible role of these compounds to act as physiological antioxidants that possess superoxide dismutase activity is discussed.

 

(REFERENCE 16 OF 32)

Neurosci Lett 1997 Dec 5;238(3):135-8

Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells.

Hipkiss AR, Preston JE, Himswoth DT, Worthington VC, Abbot NJ

Molecular Biology and Biophysics Group, King’s College London, Strand, UK.

Malondialdehyde (MDA) is a deleterious end-product of lipid peroxidation. The naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in brain and innervated tissues at concentrations up to 20 mM. Recent studies have shown that carnosine can protect proteins against cross-linking mediated by aldehyde-containing sugars and glycolytic intermediates. Here we have investigated whether carnosine is protective against malondialdehyde-induced protein damage and cellular toxicity. The results show that carnosine can (1) protect cultured rat brain endothelial cells against MDA-induced toxicity and (2) inhibit MDA-induced protein modification (formation of cross-links and carbonyl groups).

 

(REFERENCE 17 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):856-61

Cardiovascular effects of carnosine.

Roberts PR, Zaloga GP

Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1009, USA.

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide found in various cells at millimolar concentration with its specific function(s) largely unknown. Our interests in therapeutic peptides led to the discovery that carnosine dramatically increases contractility when perfused into isolated rat hearts. Carnosine’s effects are not mediated by histaminic or beta-adrenergic receptors or by increasing cyclic AMP, but carnosine does cause a rise in myoplasmic Ca2+ concentration. In chemically skinned cardiac cells, carnosine releases calcium, produces contracture, and alters the contractile protein’s tension response to calcium. Carnosine also acts directly on the ryanodine receptor calcium release channel producing large increases in open state probability and dwelltime. In this manuscript, we will review studies which provide a basis for considering carnosine a modulator of calcium-regulated proteins in cardiac muscle cells and consequently an important determinant of contractility and cardiac function.

 

(REFERENCE 18 OF 32)

Biochemistry (Mosc) 2000 Jul;65(7):766-70

A Re-evaluation of the antioxidant activity of purified carnosine.

Decker EA, Livisay SA, Zhou S

Dept. of Food Science, Chenoweth Lab, University of Massachusetts, Amherst, MA, 01003, edecker@foodsci.umass.edu.

The antioxidant activity of carnosine has been re-evaluated due to the presence of contaminating hydrazine in commercial carnosine preparations. Purified carnosine is capable of scavenging peroxyl radicals. Inhibition of the oxidation of phosphatidylcholine liposomes by purified carnosine is greater in the presence of copper than iron, a phenomenon likely to be due to the copper chelating properties of carnosine. Purified carnosine is capable of forming adducts with aldehydic lipid oxidation products. Adduct formation is greatest for alpha,beta-monounsaturated followed by polyunsaturated and saturated aldehydes. While the ability of carnosine to form adducts with aldehydic lipid oxidation products is lower than other compounds such as glutathione, the higher concentrations of carnosine in skeletal muscle are likely to make it the most important molecule that forms aldehyde adducts. Monitoring changes in carnosine concentrations in oxidizing skeletal muscle shows that carnosine oxidation does not occur until the later stages of oxidation suggesting that carnosine may not be as effective free radical scavenger in vivo as other antioxidants like alpha-tocopherol.

 

(REFERENCE 19 OF 32)

Biochem Biophys Res Commun 1998 Jul 9;248(1):28-32

Carnosine protects proteins against methylglyoxal-mediated modifications.

Hipkiss AR, Chana H

Molecular Biology and Biophysics Group, King’s College London, United Kingdom. alan.hipkiss@kcl.ac.uk

Methylglyoxal (MG) (pyruvaldehyde) is an endogenous metabolite which is present in increased concentrations in diabetics and implicated in formation of advanced glycosylation end-products (AGEs) and secondary diabetic complications. Carnosine (beta-alanyl-L-histidine) is normally present in long-lived tissues at concentrations up to 20 mM in humans. Previous studies showed that carnosine can protect proteins against aldehyde-containing cross-linking agents such as aldose and ketose hexose and triose sugars, and malon-dialdehyde, the lipid peroxidation product. Here we examine whether carnosine can protect protein exposed to MG. Our results show that carnosine readily reacts with MG thereby inhibiting MG-mediated protein modification as revealed electrophoretically. We also investigated whether carnosine could intervene when proteins were exposed to an MG-induced AGE (i.e. lysine incubated with MG). Our results show that carnosine can inhibit protein modification induced by a lysine-MG-AGE; this suggests a second intervention site for carnosine and emphasizes its potential as a possible non-toxic modulator of diabetic complications.

 

(REFERENCE 20 OF 33)

Biochim Biophys Acta 1998 Mar 12;1380(1):46-54

Protective effects of carnosine against protein modification mediated by malondialdehyde and hypochlorite.

Hipkiss AR, Worthington VC, Himsworth DT, Herwig W

Molecular Biology and Biophysics Group, King’s College London, UK.

Malondialdehyde (MDA) and hypochlorite anions are deleterious products of oxygen free-radical metabolism. The effects of carnosine, a naturally occurring dipeptide (beta-alanyl-L-histidine), on protein modification mediated by MDA and hypochlorite have been studied. MDA and hypochlorite induced formation of carbonyl groups and high molecular weight and cross-linked forms of crystallin, ovalbumin and bovine serum albumin. The presence of carnosine effectively inhibited these modifications in a concentration-dependent manner. It is proposed that relatively non-toxic carnosine and related peptides might be explored as potential therapeutic agents for pathologies that involve protein modification mediated by MDA or hypochlorite.

 

(REFERENCE 21 OF 32)

Biokhimiia (1992 Sep) 57(9):1373-7

The effect of carnosine on the liver enzyme system in the irradiated body

Naumova OV Goncharenko EN Deev LI

The effect of carnosine on post-radioactive changes in lipid peroxidation (LPO) products in blood serum and cytochrome P-450 content in liver microsomes has been studied. Per os administration of carnosine 24 hours prior to irradiation in a minimal lethal dose (7 Gr) markedly decreases the post-radioactive accumulation of LPO products in rat blood serum one hour after irradiation and fully restores the post-radioactive decrease in the cytochrome P-450 content in rat liver microsomes on day 5 after irradiation. Besides, the ability of carnosine to prevent the post-radioactive decline in the activity of UDP-glucuronyl transferase. Another key enzyme of the liver detoxifying system, has been demonstrated. The data obtained testify to the ability of carnosine to provide effective protection against post-radioactive intensification of LPO in irradiated organisms.

 

(REFERENCE 22 OF 32)

Biokhimiia (1992 Sep) 57(9):1366-72

Effect of carnosine and 4-methyluracil on the development of experimental hepatitis in rats

Silaeva SA Golenchenko VA Gavril’chak AV Onufriev MV Khatsernova BI Guliaeva NV Shekhter AB

A comparative study of the hepatoprotective effect of carnosine and 4- methyluracil under CCl4-induced acute toxic hepatitis has been carried out. The extent of liver injury and its regeneration were established from morphological data as well as from changes in the activities of alanine aminotransferase (ALT) and histidase and the bilirubin content in blood serum. Hyperlipoperoxidation in the liver and serum was assessed by the amount of TBA-active products. It was found that by day 10 of experimental hepatitis ALT and histidase levels in blood sera of untreated animals exceeded the normal values 1.3- and 3.9-fold, whereas those in the carnosine-treated group approximated the values characteristic of intact animals. The activity of serum ALT in animals treated with vitamin B12 or 4- methyluracil exceeded normal values 1.5 and 1.6 times, whereas that of histidase was 2.5 and 2.7 times as high. Carnosine and 4- methyluracil inhibited (in approximately the same degree) the formation of TBA-active products in the liver. According to morphological data, cessation of CCl4 injections was accompanied by rapid regeneration of liver tissues in all animal groups. Carnosine enhanced regenerative processes in parenchymatous and connective tissues in a far greater degree in comparison with other drugs. The mitotic index in the carnosine-treated group exceeded more than twofold the corresponding parameters in untreated animals. Possible mechanisms of carnosine action on liver repair are discussed.

 

(REFERENCE 23 OF 32)

J Nutr Sci Vitaminol (Tokyo) (1985 Dec) 31(6):607-18

Carnosine as a histidine source: transport and hydrolysis of exogeneous carnosine by rat intestine.

Tamaki N Ikeda T Fujimoto S Mizutani N

Transport and metabolism of L-carnosine (beta-alanyl-L-histidine) were studied in rat small intestine. Carnosine administered orally was found in rat serum as well as small intestine and liver, followed by an increase of histidine. At ten minutes after carnosine infusion per os, the carnosine content of the hepatic portal vein increased with the dose. On the other hand, the histidine content increased two- fold but did not vary with the dose. These results suggest that part of the carnosine administered orally is hydrolyzed to beta-alanine and histidine in the small intestine. Carnosinase activity was present in many rat tissues and was most active in kidney in the presence of Mn2+. However, in the absence of Mn2+ carnosinase activity in small intestine was found to be the same level as that of kidney. A study has been made of the distribution of carnosinase along the small intestine of adult rat. The dipeptidase was distributed along the whole length of the small intestine with maximum hydrolytic activity in the jejunum, and was localized in the cytosol of the intestinal mucosa. Antiserum prepared against carnosinase purified from kidney inhibited the activity of small intestine as well as that of kidney.

 

(REFERENCE 24 OF 32)

Lipids (1994 Jul) 29(7):461-6

Effect of dietary carnosine on plasma and tissue antioxidant concentrations and on lipid oxidation in rat skeletal muscle.

Chan WK Decker EA Chow CK Boissonneault GA

Department of Animal Sciences University of Massachusetts Amherst 01003.

The effect of dietary carnosine supplementation on plasma and tissue carnosine and alpha-tocopherol concentrations and on the formation of thiobarbituric acid reactive substances (TBARS) in rat skeletal muscle homogenates was evaluated. Plasma, heart, liver and hind leg muscle was obtained from rats fed basal semipurified diets or basal diets containing carnosine (0.0875%), alpha-tocopheryl acetate (50 ppm), or carnosine (0.0875%) plus alpha-tocopheryl acetate (50 ppm). Dietary carnosine supplementation did not increase carnosine concentrations in heart, liver and skeletal muscle. Dietary supplementation with both carnosine and alpha-tocopherol increased carnosine concentrations in liver 1.56, 1.51- and 1.51-fold as compared with diets lacking carnosine, alpha-tocopherol or both carnosine and alpha-tocopherol, respectively. Dietary supplementation with both carnosine and alpha-tocopherol also increased alpha- tocopherol concentrations in heart and liver 1-38-fold and 1.68-fold, respectively, as compared to supplementation with alpha-tocopherol alone. Dietary supplementation with carnosine, alpha-tocopherol or both carnosine and alpha-tocopherol was effective in decreasing the formation of TBARS in rat skeletal muscle homogenate, with dietary alpha-tocopherol and alpha-tocopherol plus carnosine being more effective than dietary carnosine alone. The data suggest that dietary supplementation with carnosine and alpha-tocopherol modulates some tissue carnosine and alpha-tocopherol concentrations and the formation of TBARS in rat skeletal muscle homogenates.

 

(REFERENCE 25 OF 32)

Nippon Seirigaku Zasshi (1990) 52(10):339-44

Effects of L-carnosine on blood cells and biomembrane

Nagai K Suda T Kawasaki K Yamaguchi Y

Dept. Pathophysiol. Dent. Res. Cent. Nihon Univ.

The white blood cell count in the peripheral blood decreased to 57% of the control in ddY mice after intraperitoneal administration of 3- azido-3-deoxythymidine (AZT, 500 mg/kg/day), mitomycin C (MMC, 1 mg/kg/day), or 5-fluorouracil (5-FU, 50 mg/kg/day) for 7 days or general gamma-irradiation at 35 rad. However, this reduction was significantly prevented by administering L-carnosine (CAR) or beta- alanine (beta-ALA) simultaneously or subcutaneously for 7 days from the day after irradiation, suggesting an anti-leukopenic effect of CAR. When Wistar rats were administered phenylhydrazine (PHZ, 40 mg/kg) twice 1 and 3 days before evaluation, the red blood cell count was reduced to 55% of the control. However, the reduction was to 69% in the group treated with CAR for 8 days from 9 days prior to evaluation. The hematocrit and hemoglobin level were also increased by the administration of CAR, suggesting a protective effect of the agent against hemolytic anemia. Since membrane stabilization is considered to be the mechanism of this effect lysosome-rich fraction isolated from the liver of Wistar rats were incubated in 0.2 M sucrose with CAR, and the acid phosphatase activity released into the incubation medium was measured. CAR was found to have a membrane- stabilizing effect, which reached a plateau at a final concentration of 2.5 mM. This membrane stabilizing effect was not observed with beta-ALA or L-histidine (HIS) alone at a final concentration of 5 mM, and the release of the enzyme was only slightly inhibited by HIS + beta-ALA. Therefore, CAR molecules are considered to be needed for membrane stabilization.

 

(REFERENCE 26 OF 32)

Nippon Seirigaku Zasshi (1990) 52(7):221-8

Acceleration of metabolism of stress-related substances by L- carnosine

Nagai K Suda T Kawasaki K Yamaguchi Y

Dept. Pathophysiol. Dent. Res. Cent. Nihon Univ.

Liver dysfunction was produced in the rat by injecting CCl4 subcutaneously in the back twice a week, and the effects of L- carnosine (CAR) on the resulting liver injury were examined. When CCl4 was administered to 6-week-old rats for 9 weeks, GOT and GPT values increased, but these changes were suppressed in the group concomitantly treated with CAR, indicating a protective effect of the agent on liver function. No such preventive effects of CAR was observed in 40-week-old rats, but when the CCl4 administration was discontinued after 4 weeks, GOT and GPT decreased to normal levels within 1 week of discontinuation, indicating a therapeutic effect of CAR on hepatopathy. Based on these findings, we determined the cortisone beta-reductase activity in the rat liver. The increase in this enzyme activity in the group treated with CAR indicated acceleration of cortisone metabolism. Changes of blood cortisol level and cerebral and blood noradrenaline (NA) levels were studied by exposing 6-week-old rats to electric shocks at 30 V. Cortisol released into the circulation after the stress was quickly metabolized in the CAR group and the blood level normalized after 3 hours. Following the release of NA from the brain into the circulation, the NA concentration rapidly returned to the normal level both in the brain and the blood. CAR enhanced the liver function and accelerated the metabolism of stress-related substances also in aged animals. CAR, moreover, restored the RNA contents of the mouse spleen and the immunological abilities represented by PFC reaction, which are reduced by stresses such as forced immersion, fasting, and administration of MMC.(Abstract truncated at 250 words)

 

(REFERENCE 27 OF 32)

Patol Fiziol Eksp Ter (1997 Oct-Dec)(4):17-20

Characterization of the anti-ulcer effectiveness of carnosine

Truitsina IE Shabanova ME Chikunova BZ Shavratskii VKh Formaziuk VE Sergienko VI Stvolinskii SL Boldyrev AA

The protective effect of natural dipeptide carnosine on gastric and duodenal mucosal lesions induced by acetic acid application was studied on rats. An increase in total area of the erosions on the stomach and duodenum was significantly inhibited by oral and intraperitoneal administration of carnosine. In addition, carnosine normalized the level of amino acids undergoing change during gastric mucosal injury. Histological evidence showed effective healing of the mucosal defects as a result of carnosine administration.

 

(REFERENCE 28 OF 33)

Vopr Med Khim (1993 Mar-Apr) 39(2):30-3

Correction of lipoprotein lipid peroxidation in experimental atherosclerosis with polyunsaturated fatty acids combined with antioxidants

Sdvigova AG Panasenko OM Luk’iashchenko VI Sergienko VI Lopukhin IuM

Atherosclerotic lesion of the aorta and lipid peroxidation (LPO) in blood and in lipoproteins produced in hepatocytes were studied in rabbits with experimental atherosclerosis maintained on a diet enriched in polyunsaturated fatty acids containing in corn oil (2 ml/kg daily during 30 days) and antioxidants alpha-tocopherol and carnosine (2.5 mg/kg and 50 mg/kg, respectively, daily during 30 days). This diet exhibited a hypocholesterolemic effect accompanied by approximately a 10-fold decrease of the impaired aortic area, as well as lowered content of 2-thiobarbituric acid-positive LPO products occurring in blood and, especially, in apoB lipoproteins. The antioxidant-containing diet decreased distinctly the content of LPO products both in the liver tissue homogenate and lipoprotein fraction (d < 1.065 g/cm3) produced by hepatocytes during 30-min perfusion of liver tissue. The findings suggest that the diet enriched in polyunsaturated fatty acids and antioxidants contributed to a decrease of LPO products content in the blood serum and apoB lipoproteins as well as to the inhibition of lipoprotein oxidation during their synthesis in liver cells; the diet may be recommended for the prophylaxis and treatment of atherosclerosis.

 

(REFERENCE 29 OF 32)

Behav Brain Res (1999 Feb 15) 99(1):1-6

The neurochemical basis of learning and neurocomputation: the redox theory.

Smythies J.

Department of Neuropsychiatry Institute of Neurology London UK. smythies@psy.ucsd.edu

This paper presents a new theory of the biochemical basis of learning and neurocomputation. It has now been determined that excitatory synapses on dendritic spines in the brain are continually being formed and removed. This requires a neurochemical mechanism. There is evidence to suggest that the redox state of the glutamate synapse plays an important role in determining the growth or deletion of that synapse. This redox state is controlled by the balance between the pro-oxidants hydrogen peroxide and the nitric acid radical, and the antioxidants ascorbate, carnosine, the nitrosium ion and catecholamines. Key enzymes involved are prostaglandin H synthase and nitric acid synthase. Mediation of signals of reinforcing stimuli by the catecholamines may be mediated in part by their antioxidant effect on glutamate synapses. Some experiments to test the theory are suggested.

 

(REFERENCE 30 OF 32)

Brain Res (2000 Jan 3) 852(1):56-61

Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine.

Horning MS Blakemore LJ Trombley PQ

Biomedical Research Facility Dept. of Biological Science Florida State University Tallahassee 32306 horning@neuro.fsu.edu

Zinc and copper are endogenous transition metals that can be synaptically released during neuronal activity. Synaptically released zinc and copper probably function to modulate neuronal excitability under normal conditions. However, zinc and copper also can be neurotoxic, and it has been proposed that they may contribute to the neuropathology associated with a variety of conditions, such as Alzheimer’s disease, stroke, and seizures. Recently, we demonstrated that carnosine, a dipeptide expressed in glial cells throughout the brain as well as in neuronal pathways of the visual and olfactory systems, can modulate the effects of zinc and copper on neuronal excitability. This result led us to hypothesize that carnosine may modulate the neurotoxic effects of zinc and copper as well. Our results demonstrate that carnosine can rescue neurons from zinc- and copper-mediated neurotoxicity and suggest that one function of carnosine may be as an endogenous neuroprotective agent.

 

(REFERENCE 31 OF 32)

Brain Res (1976 Jul 9) 110(2):351-60

Denervation in the primary olfactory pathway of mice. III. Effect on enzymes of carnosine metabolism.

Harding J Margolis FL

Carnosine (beta-Ala-L-His) is localized within the receptor neurons of the primary olfactory system. Carnosine synthetase, the enzyme responsible for its synthesis, is found in the primary olfactory pathway of the mouse at activities higher than that found in other body tissues and brain regions. Carnosinase, the degradative enzyme, is present at high activities, only in the olfactory epithelial portion of this pathway. Peripheral deafferentation or central denervation cause a selective decrease in the activity of carnosine synthetase in the reciprocal portion of the primary olfactory system implying specific localization within the receptor neurons. These data are consistent with a role for the dipeptide carnosine in olfactory neural transmission.

 

(REFERENCE 32 OF 32)

Cell Mol Neurobiol (1999 Feb) 19(1):45-56

Carnosine: an endogenous neuroprotector in the ischemic brain.

Stvolinsky SL Kukley ML Dobrota D Matejovicova M Tkac I Boldyrev AA

Institute of Neurology Russian Academy of Medical Sciences Moscow Russia.

1. The biological effects of carnosine, a natural hydrophilic neuropeptide, on the reactive oxygen species (ROS) pathological generation are reviewed. 2. We describe direct antioxidant action observed in the in vitro experiments. 3. Carnosine was found to effect metabolism indirectly. These effects are reflected in ROS turnover regulation and lipid peroxidation (LPO) processes. 4. During brain ischemia carnosine acts as a neuroprotector, contributing to better cerebral blood flow restoration, electroencephalography (EEG) normalization, decreased lactate accumulation, and enzymatic protection against ROS. 5. The data presented demonstrate that carnosine is a specific regulator of essential metabolic pathways in neurons supporting brain homeostasis under unfavorable conditions.