Biogerontology

, Volume 11, Issue 1, pp 103–109 | Cite as

The effect of carnosine treatment on prooxidant–antioxidant balance in liver, heart and brain tissues of male aged rats

  • A. F. Aydın
  • C. Küçükgergin
  • G. Özdemirler-Erata
  • N. Koçak-Toker
  • M. Uysal
Research article

Abstract

Carnosine (β-alanyl-l-histidine) is a dipeptide with antioxidant properties. Oxidative damage by free radicals is one of the mechanisms underlying the aging process. This study was done to investigate the effects of carnosine treatment on lipid peroxidation and antioxidant status of liver, heart, brain in male young and aged rats. At the initiation of study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to rats. At the end of this period, malondialdehyde (MDA) and diene conjugate (DC) and protein carbonyl (PC) levels, glutathione (GSH), vitamin E and vitamin C levels and Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined in tissues of carnosine-treated young and old rats. Liver and heart, but not brain MDA and DC levels increased significantly in aged rats as compared to young rats. Liver PC levels were also significantly elevated. Significant decreases in GSH and vitamin C levels and SOD activities were detected in liver of aged rats, but vitamin E levels and GSH-Px and GST activities remained unchanged. Non-enzymatic and enzymatic antioxidants did not change in heart and brain of aged rats. Carnosine treatment decreased high MDA, DC and PC levels and caused significant increases in vitamin E level and SOD activity in the liver of aged rats. There were no changes in non-enzymatic and enzymatic antioxidants in the heart and brain of carnosine-treated aged rats. In conclusion, carnosine treatment was found to be useful in the decrease of age-related oxidative stress in the liver.

Keywords

Carnosine Aging Oxidative stress Antioxidant system Rat 

References

  1. Aldini G, Facino RF, Beretta G, Carini M (2005) Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. Biofactors 24:77–87. doi:10.1002/biof.5520240109 CrossRefPubMedGoogle Scholar
  2. Beutler E, Duron O, Kelly BM (1979) Improved method for the determination of blood glutathione. Lab Clin Med 61:882–888Google Scholar
  3. Boissonneault GA, Hardwick TA, Bogardus SL, Wendy RD, Chan KM, Tatum V, Glauert HP, Chow CK, Decker EA (1998) Interactions between carnosine and vitamin E in mammary cancer risk determination. Nutr Res 18:723–733. doi:10.1016/S0271-5317(98)00058-X CrossRefGoogle Scholar
  4. Boldyrev AA (2005) Protection of proteins from oxidative stress. Ann N Y Acad Sci 1057:1–13. doi:10.1196/annals.1356.013 CrossRefGoogle Scholar
  5. Boldyrev AA, Gallant SC, Sukhich GT (1999) Carnosine, the protective, anti-aging peptide. Biosci Rep 19:581–587. doi:10.1023/A:1020271013277 CrossRefPubMedGoogle Scholar
  6. Boldyrev AA, Yuneva MO, Sorokina EV, Kramerenko GG, Fedorova TN, Konovalova GG, Lankin VZ (2001) Antioxidant systems in tissues of senescence accelerated mice. Biochemistry (Mosc) 66:1430–1437Google Scholar
  7. Buege JA, Aust JD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. doi:10.1016/S0076-6879(78)52032-6 CrossRefPubMedGoogle Scholar
  8. Desai DI (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol 105:138–147. doi:10.1016/S0076-6879(84)05019-9 CrossRefPubMedGoogle Scholar
  9. Dobrota D, Fedorova T, Stvolinsky S, Babusikova E, Likavcanova K, Drgova A, Strapkova A, Boldyrev A (2005) Carnosine protects the brain of rats and Mongalian gerbils against ischemic injury: after-stroke-effect. Neurochem Res 30:1283–1288. doi:10.1007/s11064-005-8799-7 CrossRefPubMedGoogle Scholar
  10. Fouad AA, El-Rehany MAA, Maghraby HK (2007) The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. Eur J Pharmacol 572:61–68. doi:10.1016/j.ejphar.2007.06.010 CrossRefPubMedGoogle Scholar
  11. Gallant S, Semyonova M, Yuneva M (2000) Carnosine as a potential anti-senescence drug. Biochemistry (Mosc) 65:866–868Google Scholar
  12. Habig WH, Jacoby WB (1981) Assays for differentation of glutathione s-transferases. Methods Enzymol 77:398–405. doi:10.1016/S0076-6879(81)77053-8 CrossRefPubMedGoogle Scholar
  13. Harman D (2001) Aging: overview. Ann N Y Acad Sci 928:1–21PubMedCrossRefGoogle Scholar
  14. Hipkiss AR (2000) Carnosine and protein carbonyl groups: a possible relationship. Biochemistry (Mosc) 65:907–916Google Scholar
  15. Hipkiss AR (2005) Glycation, ageing and carnosine: are carnivorous diets beneficial? Mech Ageing Dev 126:1034–1039. doi:10.1016/j.mad.2005.05.002 CrossRefPubMedGoogle Scholar
  16. Hipkiss AR (2006) Would carnosine or a carnivorous diet help suppress aging and associated pathologies? Ann N Y Acad Sci 1067:369–374. doi:10.1196/annals.1354.052 CrossRefPubMedGoogle Scholar
  17. Hipkiss AR (2007) Could carnosine or related structures suppress Alzheimer’s disease? J Alzheimers Dis 11:229–240PubMedGoogle Scholar
  18. Hipkiss AR (2008) On the enigma of carnosine’s anti-ageing actions. Exp Gerontol 44:237–242. doi:10.1016/j.exger.2008.11.001 CrossRefPubMedGoogle Scholar
  19. Hipkiss AR, Brownson C (2000) Carnosine react with carbonyl groups: another possible role for the antiageing peptide? Biogerontology 1:2217–2223. doi:10.1023/A:1010057412184 CrossRefGoogle Scholar
  20. Ibrahim W, Tatum V, Yeh CC, Hong CB, Chow CK (2008) Effects of dietary carnosine and vitamin E on antioxidant and oxidative status of rats. Int J Vitam Nutr Res 78:230–237. doi:10.1024/0300-9831.78.45.230 CrossRefPubMedGoogle Scholar
  21. Jayakumar T, Thomas PA, Geraldine P (2007) Protective effect of an extract of the oyster mushroom, Pleurotus ostreatus, on antioxidants of major organs of aged rats. Exp Gerontol 42:183–191. doi:10.1016/j.exger.2006.10.006 CrossRefPubMedGoogle Scholar
  22. Kang JH, Kim KS, Choi SY, Kwon HY, Won MH, Kang TC (2002) Protective effects of carnosine, homocarnosine and anserine against peroxyl radical-mediated Cu, Zn-superoxide dismutase modification. Biochim Biophys Acta 1570:89–96PubMedGoogle Scholar
  23. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium–deficient rat liver. Biochem Biophys Res Commun 71:952–958. doi:10.1016/0006-291X(76)90747-6 CrossRefPubMedGoogle Scholar
  24. Lee Y, Hsu C, Lin M, Yin M (2005) Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol 513:145–150. doi:10.1016/j.ejphar.2005.02.010 CrossRefPubMedGoogle Scholar
  25. Liu W, Liu T, Yin M (2008) Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. Food Chem Toxicol 46:1503–1509PubMedGoogle Scholar
  26. Maynard LM, Boissonneault GA, Chow CK, Bruckner GG (2001) High levels of dietary carnosine are associated with increased concentrations of carnosine and histidine in rat soleus muscle. J Nutr 131:287–290PubMedGoogle Scholar
  27. Mehmetçik G, Özdemirler G, Koçak-Toker N, Çevikbaş U, Uysal M (2008) Role of carnosine in preventing thioacetamide-induced liver injury in the rat. Peptides 29:425–429PubMedGoogle Scholar
  28. Mylorie AA, Collins H, Umbles C, Kyle J (1986) Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 82:512–520. doi:10.1016/0041-008X(86)90286-3 CrossRefGoogle Scholar
  29. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. doi:10.1016/0003-2697(79)90738-3 CrossRefPubMedGoogle Scholar
  30. Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol 62:3–8. doi:10.1016/0076-6879(79)62181-X CrossRefPubMedGoogle Scholar
  31. Parıldar H, Doğru-Abbasoğlu S, Mehmetçik G, Özdemirler G, Koçak-Toker N, Uysal M (2008) Lipid peroxidation potential and antioxidants in the heart tissue of β-alanine- or taurine-treated old rats. J Nutr Sci Vitaminol (Tokyo) 54:61–65. doi:10.3177/jnsv.54.61 CrossRefGoogle Scholar
  32. Parıldar-Karpuzoğlu H, Mehmetçik G, Özdemirler-Erata G, Doğru-Abbasoğlu S, Koçak-Toker N, Uysal M (2008) The effect of taurine treatment on prooxidant–antioxidant balance in livers and brains of old rats. Pharmacol Rep 60:673–678PubMedGoogle Scholar
  33. Rashid I, Van Reyk DM, Davies MJ (2007) Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett 581:1067–1070. doi:10.1016/j.febslet.2007.01.082 CrossRefPubMedGoogle Scholar
  34. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363. doi:10.1016/S0076-6879(94)33041-7 CrossRefPubMedGoogle Scholar
  35. Siqueira IR, Fochesatto C, De Andrade A, Santos M, Hagen M, Bello-Klein A, Netto CA (2005) Total antioxidant capacity is impaired in different structures from aged brain. Int J Dev Neurosci 23:663–671. doi:10.1016/j.ijdevneu.2005.03.001 CrossRefPubMedGoogle Scholar
  36. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85. doi:10.1016/0003-2697(85)90442-7 CrossRefPubMedGoogle Scholar
  37. Stuerenburg HJ, Kunze K (1999) Concentration of free carnosine (a putative membrane-protective antioxidant) in human biopsies and rat muscles. Arch Gerontol Geriatr 29:107–113. doi:10.1016/S0167-4943(99)00020-5 CrossRefPubMedGoogle Scholar
  38. Stvolinskii SL, Fedorova TN, Yuneva MO, Boldyrev AA (2003) Protective effect of carnosine on Cu, Zn-superoxide dismutase during impaired oxidative metabolism in the brain in vivo. Bull Exp Biol Med 135:130–132. doi:10.1023/A:1023855428130 CrossRefPubMedGoogle Scholar
  39. Stvolinsky SL, Dobrota D (2000) Anti-ischemic activity of carnosine. Biochemistry (Mosc) 65:849–855Google Scholar
  40. Tian L, Cai Q, Wei H (1998) Alterations of antioxidant enzymes and oxidative damage to macromolecules in different organs of rats during aging. Free Radic Biol Med 24:1477–1484. doi:10.1016/S0891-5849(98)00025-2 CrossRefPubMedGoogle Scholar
  41. Vina J, Borras C, Gambini J, Sastre J, Pallardo FV (2005) Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds. FEBS Lett 579:2541–2545. doi:10.1016/j.febslet.2005.03.090 CrossRefPubMedGoogle Scholar
  42. Wolf FI, Fasanella S, Tedesco B, Cavallini G, Donati A, Bergamini E, Cittadini A (2005) Peripheral lymphocyte 8-OHdG levels correlate with age-associated increase of tissue oxidative DNA damage in Sprague-Dawley rats. Protective effects of caloric restriction. Exp Gerontol 40:181–188. doi:10.1016/j.exger.2004.11.002 CrossRefPubMedGoogle Scholar
  43. Wong YT, Ruan R, Tay FEH (2006) Relationship between levels of oxidative DNA damage, lipid peroxidation and mitochondrial membrane potential in young and old F344 rats. Free Radic Res 40:393–402. doi:10.1080/10715760600556074 CrossRefPubMedGoogle Scholar
  44. Yuneva AO, Kramerenko GG, Vetreshchak TV, Gallant S, Boldyrev AA (2002) Effect of carnosine on Drosophila melanogaster lifespan. Bull Exp Biol Med 133:559–561. doi:10.1023/A:1020273506970 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • A. F. Aydın
    • 1
  • C. Küçükgergin
    • 1
  • G. Özdemirler-Erata
    • 1
  • N. Koçak-Toker
    • 1
  • M. Uysal
    • 1
  1. 1.Department of Biochemistry, Istanbul Medical FacultyIstanbul UniversityIstanbulTurkey

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