Skip to main content
SpringerLink
Log in

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

  • Published:
Neurochemical Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. A. A. Boldyrev A. M. Dupin A. Ya. Bunin M. A. Babizhaev S. E. Severin (1987) ArticleTitleThe antioxidative properties of carnosine, a natural histidine-containing dipeptide Biochem. Int. 15 1105–1113 Occurrence Handle3326603 Occurrence Handle1:CAS:528:DyaL1cXovVSgsQ%3D%3D

    PubMed  CAS  Google Scholar 

  2. A. A. Boldyrev A. M. Dupin E. V. Pindel S. E. Severin (1988) ArticleTitleAntioxidative properties of Histidine-containing dipeptides from skeletal muscles of vertebrates Comp. Biochem. Physiol. 89B 245–250 Occurrence Handle1:CAS:528:DyaL1cXhs1egtLs%3D

    CAS  Google Scholar 

  3. R. Kohen Y. Yamamoto K. Cundy B. Ames (1988) ArticleTitleAntioxidant activity of carnosine, homocarnosine and anserine present in muscle and brain Proc. Natl. Acad. Sci. USA 85 3175–3179 Occurrence Handle3362866 Occurrence Handle1:CAS:528:DyaL1cXitF2ns7w%3D

    PubMed  CAS  Google Scholar 

  4. O. L. Aruoma M. J. Laughton B. Halliwell (1989) ArticleTitleCarnosine, homocarnosine and anserine: Could they act as antioxidants in vivo? Biochem. J. 264 854–869

    Google Scholar 

  5. A. M. Dupin A. A. Boldyrev Yu. V. Arkhipenko V. E. Kagan (1984) ArticleTitleProtection by carnosine of Ca2+ transport from lipid peroxidation Byul. Eksp. Biol. Med. (in Russian) 98 8 186–188

    Google Scholar 

  6. E. G. Kurella O. V. Tyulina A. A. Boldyrev (1999) ArticleTitleOxidative resistance of Na,K-ATPase from brain and kidney Cell. Mol. Neurobiol. 19 133–140 Occurrence Handle10.1023/A:1006976810642 Occurrence Handle10079972 Occurrence Handle1:CAS:528:DyaK1MXhsFSitLs%3D

    Article  PubMed  CAS  Google Scholar 

  7. M. Chikira Y. Mizukami (1991) ArticleTitleStereo-specific binding of dinuclear Copper (II) complex of l-carnosine with DNA Chem. Lett. 1 189–190

    Google Scholar 

  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, USA

  9. A. A. Boldyrev R. Song D. Lawrence D. O. Carpenter (1999) ArticleTitleCarnosine protects against excitotoxic cell death independently of effects on reactive oxygen species Neuroscience 94 571–577 Occurrence Handle10.1016/S0306-4522(99)00273-0 Occurrence Handle10579217 Occurrence Handle1:CAS:528:DyaK1MXmt1entrs%3D

    Article  PubMed  CAS  Google Scholar 

  10. A. A. Boldyrev M. L. Kukley S. L. Stvolinsky I. V. Gannushkina (1996) Carnosine and free radical defense mechanisms in brain L. Packer M. G. Traber W. Xin (Eds) Natural Antioxidants: Molecular Mechanisms and Health Effects AOCS Press Champaign, II 600–613

    Google Scholar 

  11. E. Kurella M. Kukley O. Tyulina D. Dobrota M. Matejovicova V. Mezesova A Boldyrev (1997) ArticleTitleKinetic parameters of Na/K-ATPase modified by free radicals in vitro and in vivo Ann. NY Acad. Sci. 834 661–665 Occurrence Handle9405886 Occurrence Handle1:CAS:528:DyaK1cXitl2jtw%3D%3D

    PubMed  CAS  Google Scholar 

  12. S. Stvolinsky M. Kukley D. Dobrota V. Mezesova A. Boldyrev (2000) ArticleTitleCarnosine protects rats under global Ischemia Brain Res. Bull. 33 445–448

    Google Scholar 

  13. J. H. Kang K. S. Kim S. I. Choi H. Y. Kwon M. H. Won T. C. Kang (2002) ArticleTitleCarnosine and related dipeptides protect human ceruloplasmin against peroxyl radical-mediated modification Mol. Cells 13 498–502 Occurrence Handle12132593 Occurrence Handle1:CAS:528:DC%2BD38Xlt1SksLg%3D

    PubMed  CAS  Google Scholar 

  14. S. Y. Choi H. Y. Kwon O. B. Kwon J. H. Kang (1999) ArticleTitleHydrogen peroxide-mediated Cu, Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine Biochim. Biophys. Acta. 1472 651–657 Occurrence Handle10564779 Occurrence Handle1:CAS:528:DyaK1MXntlClt7o%3D

    PubMed  CAS  Google Scholar 

  15. S. L. Stvolinsky T. N. Fedorova M. O. Yuneva A. A. Boldyrev (2003) ArticleTitleProtection of Cu/Zn-SOD by carnosine under conditions of oxidative stress in vivo Byul. Eksp. Biol. Med. (in Russian). 135 151–154

    Google Scholar 

  16. W. A. Pulsinelli J. B. Brierley (1979) ArticleTitleA new model of bilateral hemispheric Ischemia in the un-anaesthetized rat Stroke 10 267–272 Occurrence Handle37614 Occurrence Handle1:STN:280:CSaB38nisFM%3D

    PubMed  CAS  Google Scholar 

  17. M. F. Beal (1994) ArticleTitleNeurochemistry and toxin models in Huntington’s disease Curr. Opin. Neurol. 7 542–547 Occurrence Handle7866587 Occurrence Handle1:STN:280:ByqC2s%2FpsVc%3D

    PubMed  CAS  Google Scholar 

  18. M. C. Guyot P. Hantaraye R. Dolan S. Palfi M. Maziere E. Brouillet (1997) ArticleTitleQuantifiable bradykinesia, gait abnormalities and Huntington’s disease-like striated lesions in rats chronically treated with 3-Nitropropionic acid Neuroscience 79 45–56 Occurrence Handle10.1016/S0306-4522(96)00602-1 Occurrence Handle9178864 Occurrence Handle1:CAS:528:DyaK2sXjvVahs7s%3D

    Article  PubMed  CAS  Google Scholar 

  19. T. Kirino T. A. Tamira K. Sano (1985) ArticleTitleSelective vulnerability of the hippocampus to Ischemia––reversible and Irreversible types of Ischemic cell damage Prog. Brain Res. 63 39–58 Occurrence Handle3835581 Occurrence Handle1:STN:280:BimB3svhvFI%3D

    PubMed  CAS  Google Scholar 

  20. H. Imon A. Mitani Y. Andou T. Arai K. Kataoka (1991) ArticleTitleDelayed neuronal death is induced without postischemic hyperexcitability: Continuous multiple-unit recording from Ischemic CA1 neurons J. Cerebr. Blood Fl. Metab. 11 819–823 Occurrence Handle1:STN:280:By6A2c%2FoslU%3D

    CAS  Google Scholar 

  21. C.P. McGrow (1977) ArticleTitleExperimental cerebral infarction effects of pentobarbital in Mongolian gerbils Arch. Neurol. 34 334–336

    Google Scholar 

  22. T. N. Fedorova A. A. Boldyrev I. V. Gannushkina (1999) ArticleTitleLipid peroxidation during experimental brain Ischemia Biochemistry (Moscow) 64 94–98

    Google Scholar 

  23. Y. A. Vladimirov (1966) Studies of antioxidant activity by measuring chemiluminescence kinetics L. Packer M. G. Traber W. Xin (Eds) Natural Antioxidants: Molecular Mechanisms and Health Effects AOCS Press Champaign, II 125–144

    Google Scholar 

  24. K. Umemura K. Wada T. Uematsu A Mizuno M. Nakashima (1994) ArticleTitleEffect of 21-aminosteroid lipid peroxidation inhibitor, U 74006F, in the rat middle cerebral artery occlusion model Eur. J. Pharmacol. 251 69–74 Occurrence Handle10.1016/0014-2999(94)90444-8 Occurrence Handle8137871 Occurrence Handle1:CAS:528:DyaK2cXhsFCjs7w%3D

    Article  PubMed  CAS  Google Scholar 

  25. Z. Guo A. Ersoz A. Butterfield M. P. Mattson (2000) ArticleTitleBeneficial 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 acid J. Neurochem. 75 314–320 Occurrence Handle10.1046/j.1471-4159.2000.0750314.x Occurrence Handle10854276 Occurrence Handle1:CAS:528:DC%2BD3cXkt12qtLY%3D

    Article  PubMed  CAS  Google Scholar 

  26. M. Lafon-Casal S. Pietry M. Culcasi J. Bockaert (1993) ArticleTitleNMDA-dependent superoxide production and neurotoxicity Nature 364 535–537

    Google Scholar 

  27. Z. Binienda C. Simmons S. Hussain W. Slikker S. F. Ali (1998) ArticleTitleEffect of acute exposure to 3-Nitropropionic acid on activities of endogeneous antioxidants in the rat brain Neurosci. Lett. 251 173–176 Occurrence Handle10.1016/S0304-3940(98)00539-4 Occurrence Handle9726371 Occurrence Handle1:CAS:528:DyaK1cXkslyltLc%3D

    Article  PubMed  CAS  Google Scholar 

  28. J. B. Shulz D. R. Henshaw U. MacGarwey M. F. Beal (1996) ArticleTitleInvolvement of oxidative stress in 3-Nitropropionic acid neurotoxicity Neurochem. Int. 29 167–171

    Google Scholar 

  29. M. A. Fontain La J. W. Geddes A. Banks A. Butterfield (2000) ArticleTitleEffect of exogenous and endogenous antioxidants on 3-nitropropionic acid-induced in vivo oxidative stress and striatal lesions: Insights into Huntington’s disease J. Neurochem. 75 1709–1715

    Google Scholar 

  30. A. A. Boldyrev S. E. Severin (1990) ArticleTitleThe Histidine-containing dipeptides, carnosine and anserine: Distribution, properties and biological significance Adv. Enzyme Reg. 30 175–194 Occurrence Handle1:CAS:528:DyaK3cXlvVKlsLY%3D

    CAS  Google Scholar 

  31. P. Nicotera (2000) Apoptosois and neurodegeneration: Role of caspases J. Krieglstein S. Klumpp (Eds) Pharmacology of Cerebral Ischemia Med. Pharm. Sci. Publ Stuttgart 3–9

    Google Scholar 

  32. G. I. Klebanov Yu. O. Teselkin I. V. Babenkova I. N. Popov G. Levin O. V. Tyuina A. A. Boldyrev Yu. A. Vladimirov (1997) ArticleTitleEvidence for a direct interaction of superoxide anion radical with carnosine Biochem. Mol. Biol. Int. 43 99–106 Occurrence Handle9315287 Occurrence Handle1:CAS:528:DyaK2sXnt12ktr8%3D

    PubMed  CAS  Google Scholar 

  33. L. V. Chasovnikova V. E. Formazyuk V. I. Sergienko A. A. Boldyrev S. E. Severin (1990) ArticleTitleAntioxidant properties of carnosine and other drugs Biochem. Int. 20 1097–1103 Occurrence Handle2369412 Occurrence Handle1:CAS:528:DyaK3cXkvFWnsrg%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia

    Dusan Dobrota, Eva Babusikova, Katarina Likavcanova, Anna Drgova & Adriana Strapkova

  2. Laboratory of Neurochemistry, Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia

    Tatiana Fedorova, Sergey Stvolinsky & Alexander Boldyrev

  3. Department of Biochemistry, International Biotechnological Center of M.V. Lomonosov Moscow State University, Moscow, Russia

    Alexander Boldyrev

  4. Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, 03601, Martin, Slovakia

    Dusan Dobrota

Authors
  1. Dusan Dobrota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatiana Fedorova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sergey Stvolinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eva Babusikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katarina Likavcanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Drgova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adriana Strapkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexander Boldyrev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dusan Dobrota.

Additional information

Special issue dedicated to Dr. Bernd Hamprecht

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dobrota, D., Fedorova, T., Stvolinsky, S. et al. Carnosine Protects the Brain of Rats and Mongolian Gerbils against Ischemic Injury: After-Stroke-Effect. Neurochem Res 30, 1283–1288 (2005). https://doi.org/10.1007/s11064-005-8799-7

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-005-8799-7

Key words

Search

Navigation