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Amino Acids

, Volume 43, Issue 1, pp 165–170 | Cite as

Carnosine and its (S)-Trolox™ derivative protect animals against oxidative stress

  • S. Stvolinsky
  • K. Toropova
  • M. Gordeeva
  • V. Kazey
  • T. Sato
  • K. Meguro
  • A. BoldyrevEmail author
Original Article

Abstract

The novel synthetic derivative of carnosine, (S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-β-alanyl-l-histidine (S-Trolox™-Carnosine, STC) increases the resistance of rats to experimental acute hypobaric hypoxia (AHH) thus protecting brain from the oxidative damage. This effect is accompanied by better preservation of the acquired skills in Morris water maze possibly by increasing efficiency of the brain antioxidant system. In addition, STC caused an increase in life span of both male and female fruit fly Drosophila melanogaster whereas carnosine increased life span only in male fruit flies. The results indicate that development of the drug based on STC could be beneficial in neurology and gerontology.

Keywords

Carnosine Trolox™ Acute hypobaric hypoxia Oxidative stress Brain Antioxidant defense 

Notes

Acknowledgments

Supported by RFBR Grants ## 09-04-00505, 10-04-01461, and 11-04-00906.

References

  1. Aldini G, Orioli M, Rossoni G, Savi F, Braidotti P, Vistoli G, Yeum KJ, Negrisoli G, Carini M (2011) The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats. J Cell Mol Med 15(6):1339–1354PubMedCrossRefGoogle Scholar
  2. Aruoma O, Laughton M, Halliwell B (1989) Carnosine, homocarnosine and anserine: could they act as antioxidants in vivo? Biochem J 264:863–869PubMedGoogle Scholar
  3. Biegel A, Knütter I, Hartrodt B, Gebauer S, Theis S, Luckner P, Kottra G, Rastetter M, Zebisch K, Thondorf I, Daniel H, Neubert K, Brandsch M (2006) The renal type H+/peptide symporter PEPT2: structure-affinity relationships. Amino Acids 31(2):137–156PubMedCrossRefGoogle Scholar
  4. Boldyrev AA (1993) Does carnosine possess direct antioxidant activity? Int J Biochem 25:1101–1107PubMedCrossRefGoogle Scholar
  5. Boldyrev AA (2003) Significance of reactive oxygen species for neuronal function. In: Tomasi A et al (eds) Free radicals, NO, and Inflammation: molecular, biochemical and clinical aspects. IOS Press, The Netherlands, pp 153–169Google Scholar
  6. Boldyrev A (2005) Protection of proteins from oxidative stress: a new illusion or a novel strategy? Ann N Y Acad Sci 1057:193–205PubMedCrossRefGoogle Scholar
  7. Boldyrev A (2006) Carnosine and protection of cells and tissues against oxidative stress, NovaPubl., NYGoogle Scholar
  8. Boldyrev AA, Dupin AM, Bunin AYa, Babizhaev MA, Severin SE (1987) The antioxidative properties of carnosine, a natural histidine containing dipeptide. Biochem Int 15:1105–1113PubMedGoogle Scholar
  9. Boldyrev AA, Stvolinsky SL, Tyulina OV, Koshelev VB, Hori N, Carpenter D (1997) Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol 17(2):259–271PubMedCrossRefGoogle Scholar
  10. Boldyrev A, Song R, Lawrence D, Carpenter DO (1999) Carnosine protects against excitotoxic cell death independently of effects on reactive oxygen species. Neuroscience 94:571–577PubMedCrossRefGoogle Scholar
  11. Boldyrev A, Stvolinsky S, Fedorova T, Suslina Z (2010) Carnosine as a natural antioxidant and geroprotector: from molecular mechanisms to clinical trials. Rejuv Res 13(2–3):156–158CrossRefGoogle Scholar
  12. Dobrota D, Fedorova T, Stepanova M, Babusikova E, Statelova D, Tatarkova Z, Stvolinsky S, Boldyrev A (2010) Oxidative stress, induced in rat brain by a combination of 3-nitropropionic acid and global ischemia. J Clin Exp Med 3:144–152Google Scholar
  13. Feldman LA, Shapiro ML, Nalbantoglu J (2010) A novel, rapidly acquired and persistent spatial memory task that induces immediate early gene expression. Behav Brain Funct 6:35–46PubMedCrossRefGoogle Scholar
  14. Gallant S, Kukley M, Stvolinsky S, Bulygina E, Boldyrev A (2000) Effect of carnosine on rats under experimental brain ischemia. Tohoku J Exp Med 191:85–99PubMedCrossRefGoogle Scholar
  15. Gupta S, Sharma SS (2006) Neuroprotective effects of Trolox™ in global cerebral ischemia in gerbils. Biol Pharm Bull 29:957–961PubMedCrossRefGoogle Scholar
  16. Hipkiss A (2009) Carnosine and its possible roles in nutrition and health. Adv Food Nutr Res 57:87–154PubMedCrossRefGoogle Scholar
  17. Iliadi KG, Iliadi NN, Boulianne GL (2009) Regulation of Drosophila life-span: effect of genetic background, sex, mating and social status. Exp Gerontol 44:546–553PubMedCrossRefGoogle Scholar
  18. Kang JH (2010) Protective effects of carnosine and homocarnosine on ferritin and hydrogen peroxide-mediated DNA damage. BMB Rep 43(10):683–687PubMedCrossRefGoogle Scholar
  19. Kohen R, Yamamoto Y, Cundy K, Ames BN (1988) Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc Natl Acad Sci USA 85:3175–3179PubMedCrossRefGoogle Scholar
  20. Koren E, Kohen R, Ginsburg I (2010) Polyphenols enhance total oxidant-scavenging capacities of human blood by binding to red blood cells. Exp Biol Med 235:689–699CrossRefGoogle Scholar
  21. Kosolapov VA, Spasov AA, Tibirjkov EV (2009) Antioxidant and membrane protector properties of Trolox™. Exptl Clin Pharmacol 2:47–50Google Scholar
  22. Leinsoo T, Abe H, Boldyrev A (2006) Carnosine and related compounds protect double-helices DNA against oxidative injury. J Evol Biochem Physiol 42:453–456CrossRefGoogle Scholar
  23. Lints FA, Bourgois M, Delalieux A, Stoll J, Lints CV (1983) Does the female life span exceed that of the male? A study in Drosophila melanogaster. Gerontology 29:336–352PubMedCrossRefGoogle Scholar
  24. Miller DJ, O’Dowd A (2000) Vascular smooth muscle actions of carnosine as its zinc complex are mediated by histamine H(1) and H(2) receptors. Biochemistry (Mosc) 65(7):798–806Google Scholar
  25. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60PubMedCrossRefGoogle Scholar
  26. Schlesier K, Harwat M, Bőhm V, Bitsch R (2002) Assessment of antioxidant activity by using different in vitro methods. Free Rad Res 36:177–187CrossRefGoogle Scholar
  27. Sharma SS, Kaundal RK (2007) Neuroprotective effects of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox™), an antioxidant in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Neurol Res 29(3):304–309PubMedCrossRefGoogle Scholar
  28. Stvolinsky SL, Kukley ML, Dobrota D, Matejovicova M, Tkac I, Boldyrev AA (1999) Carnosine: an endogeneous neuroprotector in ischemic brain. Cell Molec Neurobiol 19:45–56PubMedCrossRefGoogle Scholar
  29. Stvolinsky SL, Bulygina ER, Fedorova TN, Meguro K, Sato T, Tyulina OV, Abe H, Boldyrev AA (2010a) Biological activity of novel synthetic derivatives of carnosine. Cell Mol Neurobiol 30(3):395–404PubMedCrossRefGoogle Scholar
  30. Stvolinsky S, Antipin M, Meguro K, Sato T, Abe H, Boldyrev A (2010b) Effect of carnosine and its Trolox™-modified derivatives on lifespan of Drosophila melanogaster. Rejuv Res 13(4):453–457CrossRefGoogle Scholar
  31. Tanida M, Niijima A, Fukuda Y, Sawai H, Tsuruoka N, Shen J, Yamada S, Kiso Y, Nagai K (2005) Dose-dependent effects of l-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats. Am J Physiol Regul Integr Comp Physiol 288(2):R447–R455PubMedCrossRefGoogle Scholar
  32. Yuneva AO, Kramarenko GG, Vetreshchak TV, Gallant S, Boldyrev AA (2002) Effect of carnosine on Drosophila melanogaster life span. Bull Exp Biol Med 133(6):559–661CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • S. Stvolinsky
    • 1
  • K. Toropova
    • 2
  • M. Gordeeva
    • 2
  • V. Kazey
    • 3
  • T. Sato
    • 4
  • K. Meguro
    • 4
  • A. Boldyrev
    • 1
    • 2
    Email author
  1. 1.Research Center of NeurologyMoscowRussia
  2. 2.Moscow State UniversityMoscowRussia
  3. 3.Chemical Diversity Research InstituteKhimkiRussia
  4. 4.Hamari Chemicals, LtdOsakaJapan

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