Advertisement

Neurochemical Research

, Volume 30, Issue 10, pp 1283–1288 | Cite as

Carnosine Protects the Brain of Rats and Mongolian Gerbils against Ischemic Injury: After-Stroke-Effect

  • Dusan Dobrota
  • Tatiana Fedorova
  • Sergey Stvolinsky
  • Eva Babusikova
  • Katarina Likavcanova
  • Anna Drgova
  • Adriana Strapkova
  • Alexander Boldyrev
Article

Abstract

Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7–14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.

Key words

Brain ischemia oxidative stress antioxidant activity carnosine Mongolian gerbils rats 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Boldyrev, A. A., Dupin, A. M., Bunin, A. Ya., Babizhaev, M. A., Severin, S. E. 1987The antioxidative properties of carnosine, a natural histidine-containing dipeptideBiochem. Int.1511051113PubMedGoogle Scholar
  2. 2.
    Boldyrev, A. A., Dupin, A. M., Pindel, E. V., Severin, S. E. 1988Antioxidative properties of Histidine-containing dipeptides from skeletal muscles of vertebratesComp. Biochem. Physiol.89B245250Google Scholar
  3. 3.
    Kohen, R., Yamamoto, Y., Cundy, K., Ames, B. 1988Antioxidant activity of carnosine, homocarnosine and anserine present in muscle and brainProc. Natl. Acad. Sci. USA8531753179PubMedGoogle Scholar
  4. 4.
    Aruoma, O. L., Laughton, M. J., Halliwell, B. 1989Carnosine, homocarnosine and anserine: Could they act as antioxidants in vivo?Biochem. J.264854869Google Scholar
  5. 5.
    Dupin, A. M., Boldyrev, A. A., Arkhipenko, Yu. V., Kagan, V. E. 1984Protection by carnosine of Ca2+ transport from lipid peroxidationByul. Eksp. Biol. Med. (in Russian) 988186188Google Scholar
  6. 6.
    Kurella, E. G., Tyulina, O. V., Boldyrev, A. A. 1999Oxidative resistance of Na,K-ATPase from brain and kidneyCell. Mol. Neurobiol.19133140CrossRefPubMedGoogle Scholar
  7. 7.
    Chikira, M., Mizukami, Y. 1991Stereo-specific binding of dinuclear Copper (II) complex of l-carnosine with DNAChem. Lett.1189190Google Scholar
  8. 8.
    Boldyrev, A. A., Leinsoo, T. A., and Abe, H. 2002. Methylation of Neuropeptide Carnosine Modifies its Protecting but not Antioxidant Properties. 33rd Annual Meeting Soc. Neurosci., Abstract #671.7, Washington, DC, USAGoogle Scholar
  9. 9.
    Boldyrev, A. A., Song, R., Lawrence, D., Carpenter, D. O. 1999Carnosine protects against excitotoxic cell death independently of effects on reactive oxygen speciesNeuroscience94571577CrossRefPubMedGoogle Scholar
  10. 10.
    Boldyrev, A. A., Kukley, M. L., Stvolinsky, S. L., Gannushkina, I. V. 1996Carnosine and free radical defense mechanisms in brainPacker, L.Traber, M. G.Xin, W. eds. Natural Antioxidants: Molecular Mechanisms and Health EffectsAOCS PressChampaign, II600613Google Scholar
  11. 11.
    Kurella, E., Kukley, M., Tyulina, O., Dobrota, D., Matejovicova, M., Mezesova, V., Boldyrev, A 1997Kinetic parameters of Na/K-ATPase modified by free radicals in vitro and in vivoAnn. NY Acad. Sci.834661665PubMedGoogle Scholar
  12. 12.
    Stvolinsky, S., Kukley, M., Dobrota, D., Mezesova, V., Boldyrev, A. 2000Carnosine protects rats under global IschemiaBrain Res. Bull.33445448Google Scholar
  13. 13.
    Kang, J. H., Kim, K. S., Choi, S. I., Kwon, H. Y., Won, M. H., Kang, T. C. 2002Carnosine and related dipeptides protect human ceruloplasmin against peroxyl radical-mediated modificationMol. Cells13 498502PubMedGoogle Scholar
  14. 14.
    Choi, S. Y., Kwon, H. Y., Kwon, O. B., Kang, J. H. 1999Hydrogen peroxide-mediated Cu, Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserineBiochim. Biophys. Acta.1472651657PubMedGoogle Scholar
  15. 15.
    Stvolinsky, S. L., Fedorova, T. N., Yuneva, M. O., Boldyrev, A. A. 2003Protection of Cu/Zn-SOD by carnosine under conditions of oxidative stress in vivoByul. Eksp. Biol. Med. (in Russian).135151154Google Scholar
  16. 16.
    Pulsinelli, W. A., Brierley, J. B. 1979A new model of bilateral hemispheric Ischemia in the un-anaesthetized ratStroke10267272PubMedGoogle Scholar
  17. 17.
    Beal, M. F. 1994Neurochemistry and toxin models in Huntington’s diseaseCurr. Opin. Neurol.7542547PubMedGoogle Scholar
  18. 18.
    Guyot, M. C., Hantaraye, P., Dolan, R., Palfi, S., Maziere, M., Brouillet, E. 1997Quantifiable bradykinesia, gait abnormalities and Huntington’s disease-like striated lesions in rats chronically treated with 3-Nitropropionic acidNeuroscience794556CrossRefPubMedGoogle Scholar
  19. 19.
    Kirino, T., Tamira, T. A., Sano, K. 1985Selective vulnerability of the hippocampus to Ischemia––reversible and Irreversible types of Ischemic cell damageProg. Brain Res.633958PubMedGoogle Scholar
  20. 20.
    Imon, H., Mitani, A., Andou, Y., Arai, T., Kataoka, K. 1991Delayed neuronal death is induced without postischemic hyperexcitability: Continuous multiple-unit recording from Ischemic CA1 neuronsJ. Cerebr. Blood Fl. Metab.11819823Google Scholar
  21. 21.
    McGrow, C.P. 1977Experimental cerebral infarction effects of pentobarbital in Mongolian gerbilsArch. Neurol.34334336Google Scholar
  22. 22.
    Fedorova, T. N., Boldyrev, A. A., Gannushkina, I. V. 1999Lipid peroxidation during experimental brain IschemiaBiochemistry (Moscow)649498Google Scholar
  23. 23.
    Vladimirov, Y. A. 1966Studies of antioxidant activity by measuring chemiluminescence kineticsPacker, L.Traber, M. G.Xin, W. eds. Natural Antioxidants: Molecular Mechanisms and Health EffectsAOCS PressChampaign, II125144Google Scholar
  24. 24.
    Umemura, K., Wada, K., Uematsu, T., Mizuno, A, Nakashima, M. 1994Effect of 21-aminosteroid lipid peroxidation inhibitor, U 74006F, in the rat middle cerebral artery occlusion modelEur. J. Pharmacol.251 6974CrossRefPubMedGoogle Scholar
  25. 25.
    Guo, Z., Ersoz, A., Butterfield, A., Mattson, M. P. 2000Beneficial effects of dietary restriction on general cortical synaptic terminals: preservation of glucose and glutamate transport and mitochondrial function after exposure to amyloid (-peptide, Iron, and 3-nitropropionic acidJ. Neurochem.75314320CrossRefPubMedGoogle Scholar
  26. 26.
    Lafon-Casal, M., Pietry, S., Culcasi, M., Bockaert, J. 1993NMDA-dependent superoxide production and neurotoxicityNature364535537Google Scholar
  27. 27.
    Binienda, Z., Simmons, C., Hussain, S., Slikker, W., Ali, S. F. 1998Effect of acute exposure to 3-Nitropropionic acid on activities of endogeneous antioxidants in the rat brainNeurosci. Lett.251173176CrossRefPubMedGoogle Scholar
  28. 28.
    Shulz, J. B., Henshaw, D. R., MacGarwey, U., Beal, M. F. 1996Involvement of oxidative stress in 3-Nitropropionic acid neurotoxicityNeurochem. Int.29167171Google Scholar
  29. 29.
    Fontain La, M. A., Geddes, J. W., Banks, A., Butterfield, A. 2000Effect of exogenous and endogenous antioxidants on 3-nitropropionic acid-induced in vivo oxidative stress and striatal lesions: Insights into Huntington’s diseaseJ. Neurochem.7517091715Google Scholar
  30. 30.
    Boldyrev, A. A., Severin, S. E. 1990The Histidine-containing dipeptides, carnosine and anserine: Distribution, properties and biological significanceAdv. Enzyme Reg.30175194Google Scholar
  31. 31.
    Nicotera, P. 2000Apoptosois and neurodegeneration: Role of caspasesKrieglstein, J.Klumpp, S. eds. Pharmacology of Cerebral IschemiaMed. Pharm. Sci. PublStuttgart39Google Scholar
  32. 32.
    Klebanov, G. I., Teselkin, Yu. O., Babenkova, I. V., Popov, I. N., Levin, G., Tyuina, O. V., Boldyrev, A. A., Vladimirov, Yu. A. 1997Evidence for a direct interaction of superoxide anion radical with carnosineBiochem. Mol. Biol. Int.43 99106PubMedGoogle Scholar
  33. 33.
    Chasovnikova, L. V., Formazyuk, V. E., Sergienko, V. I., Boldyrev, A. A., Severin, S. E. 1990Antioxidant properties of carnosine and other drugsBiochem. Int.2010971103PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Dusan Dobrota
    • 1
    • 4
  • Tatiana Fedorova
    • 2
  • Sergey Stvolinsky
    • 2
  • Eva Babusikova
    • 1
  • Katarina Likavcanova
    • 1
  • Anna Drgova
    • 1
  • Adriana Strapkova
    • 1
  • Alexander Boldyrev
    • 2
    • 3
  1. 1.Department of Medical BiochemistryJessenius Faculty of Medicine, Comenius UniversityMartinSlovakia
  2. 2.Laboratory of NeurochemistryInstitute of Neurology, Russian Academy of Medical SciencesMoscowRussia
  3. 3.Department of BiochemistryInternational Biotechnological Center of M.V. Lomonosov Moscow State UniversityMoscowRussia
  4. 4.Department of Medical BiochemistryJessenius Faculty of Medicine, Comenius UniversityMartinSlovakia

Personalised recommendations