Antonova E., Ilyukha V., Sergina S. Antioxidant defense system in hibernating mammals // Principy èkologii. 2015. № 2. P. 4‒20. DOI: 10.15393/

Issue № 2

Analytical review


Antioxidant defense system in hibernating mammals

   Ekaterina Petrovna
Institute of Biology of Karelian Research Centre, Russian Academy of Sciences,
Institute of Biology of Karelian Research Centre, Russian Academy of Sciences,
Institute of Biology of Karelian Research Centre, Russian Academy of Sciences,
antioxidant system
Summary: Hibernation is one of the most striking examples of mammals’ phenotypic flexibility, allowing them to survive at low temperatures and in the conditions of insufficient food and water. During the torpor there is a decrease in both body temperature and metabolic rate that is accompanied by slowing respiration, significant drop of oxygen consumption as well as by the reduction of cerebral blood circulation and heart rate. In spite of a number of physiological adaptations to hibernation, the arousal from torpor is accompanied by the oxidative stress caused by the enormous rise of oxygen consumption. In these conditions, the antioxidant defense system which provides harmless transfer from torpor to arousal and vice versa, i.e., without any tissues’ oxidative damage, becomes especially important. Up to date, it is not fully elucidated how the antioxidant system acts during the periods of hibernation, but it deserves careful attention. In the review the information about the use of different strategies of antioxidant protection during hibernation in small mammals was collected

© Petrozavodsk State University

Received on: 29 January 2015
Published on: 13 April 2015


Anufriev A. I. Mechanisms of hibernation of Yakutia small mammals. Novosibirsk: SO RAN, 2008. 158 p.

Anufriev A. I. Revin Yu. V. Bioenergetics of bats (Chiroptera: Vespertilionidae) hibernation in Yakutia, Plecotus et al. 2006. No. 9. P. 8–17.

Vladimirov Yu. A. Free radicals, Vestn. Rop. AMN. 1998. No. 7. P. 43–51.

Galancev V. P. Evolution of diving animals adaptations. Ecological and morphological aspects. L.: Nauka, 1977. 191 p.

Zenkov N. K. Lankin V. Z. Men'schikova E. B. Oxidative stress: biochemical and pathophysiological aspects. M.: MAIK «Nauka/Interperiodika», 2001. 343 p.

Zenkov N. K. Men'schikova E. B. Reactive oxygen species in biological systems, Usp. sovrem. biol. 1993. T. 113, No. 3. P. 286–296.

Kalabuhov N. I. Estivation of ground squirrels (С. fulvus и С. pygmaeus), Tr. lab. eksperiment. biologii Mosk. Zooparka. 1929. T. 5. P. 163–176.

Kogan A. X. Phagocyte-dependent oxygen free radical mechanisms of autoaggression in the internal diseases’ pathogenesis, Vestnik RAMN. 1999. No. 2. P. 3–10.

Serebryannikova E. T. Veksler Ya. I. Influence of the adaptation to hypothermia on the fatty acid composition of lipids in rats tissues, Ukr. biohim. zhurn. 1977. T. 49, No. 2. P. 16–21.

Skulachev V. P. Alternative functions of cellular respiration, Sorosovskiy obrazovatel'nyy zhurnal. 1998. No. 8. P. 2–7.

Niel'sen K. Scaling. Why is animal size so important?: Per. s angl. M.: Mir, 1987. 259 p.

Aarseth J. J., Froiland E., Jorgensen E. H. Melatonin implantation during spring and summer does not affect the seasonal rhythm of feeding in anadromous Arctic charr (Salvelinus alpinus), Polar Biol. 2010. Vol. 33. P. 379–388.

Allan M. E., Storey K. B. Expression of NF-kB and downstream antioxidant genes in skeletal muscle of hibernating ground squirrels, Spermophilus tridecemlineatus, Cell. Biochem. Funct. 2012. Vol. 30. P. 166–174.

Austad S. N. Diverse aging rates in metazoans: targets for functional genomics, Mech. Ageing Dev. 2005. Vol. 126. P. 43–49.

Barja G., Cadenas S., Rojas C., Pérez-Campo R. et al. Low mitochondrial free radical production per unit O 2 consumption can explain the simultaneous presence of high longevity and high metabolic rate in birds, Free Radic. Res. 1994. Vol. 21. P. 317–328.

Bouma H. R., Carey H. V., Kroese F. G. M. Hibernation: the immune system at rest?, J. Leukoc. Biology. 2010a. Vol. 88. P. 619–624.

Bouma N. R., Strijkstra F. M., Boerema A. S., Deelman L. E. et al. Bllod cell dynamics during hibernation in the Europian Ground Squirrel, Vet. Immunol. Immunopathol. 2010b. Vol. 136. P. 319–323.

Braulke L. J., Heldmaier G., Berriel Diaz M., Rozman J. et al. Seasonal changes of myostatin expression and its relation to body mass acclimation in the Djungarian hamster, Phodopus sungorus, J. Exp. Zool. 2010. Vol. 313. P. 548–556.

Breukelen F., Martin S. L. Invited Review: Molecular adaptations in mammalian hibernators: unique adaptations or generalized responses?, J. Appl. Physiol. 2002. Vol. 92. R. 2640–2647.

Brooks N. E., Myburgh K. H., Storey K. B. Myostatin levels in skeletal muscle of hibernating ground squirrels, J. Exp. Biol. 2011. Vol. 214. P. 2522–2527.

Brooks S. P., Storey K. B. Mechanisms of glycolytic control during hibernation in the ground squirrel Spermophilus lateralis, J. Comp. Physiol. 1992. Vol. 162. P. 23–28.

Brown J. C., Chung D. J., Belgrave K. R., Staples J. F. Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels, Am. J. Physiol. Regul. Integr. Comp. Physiol. 2012. Vol. 302. No. 1. R. 15–28.

Brune B., Zhou J. Nitric oxide, oxidative stress, and apoptosis, Kidney Int. 2003. Vol. 84. P. 22–24.

Brunet-Rossini A. K. Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals, Mech. Ageing Dev. 2004. Vol. 125. P. 11–20.

Brunet-Rossinni A. K., Austad S. N. Ageing studies on bats: a review, Biogerontology. 2004. Vol. 5. P. 211–222.

Buck C. L., Barnes B. M. Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernator, Am. J. Physiol. Regulatory Integrative Comp. Physiol. 2000. Vol. 279. P. 255–262.

Buck M. J., Squire T. L., Andrews M. T. Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal, Physiol. Genomics. 2002. Vol. 8. P. 5–13.

Carey H. V., Andrews M. T., Martin S. L. Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature, Physiol. Rev. 2003. Vol. 83. P. 1153–1181.

Carey H. V., Frank C. L., Seifert J. Hibernation induces oxidative stress and activation of NF-κB in ground squirrel intestine, J. Comp. Physiol. 2000. Vol. 170B. P. 551–559.

Clark B. C. In vivo alterations in skeletal muscle form and function after disuse atrophy, Med. Sci. Sports Exerc. 2009. Vol. 41. P. 1869–1875.

Conde-Perezprina J. C., Luna-Lopez A., Gonzalez-Puertos V. Y., Zenteno-Savın T. et al. DNA MMR systems, microsatellite instability and antioxidant activity variations in two species of wild bats: Myotis velifer and Desmodus rotundus, as possible factors associated with longevity, Age. 2012. Vol. 34. No. 6. P. 1473–1492.

Cui J., Pan Y. H., Zhang Y., Jones G. et al. Progressive pseudogenization: vitamin C synthesis and its loss in bats, Mol. Biol. Evol. 2011. Vol. 28. P. 1025–1031.

Dave K. R., Christian S. L., Perez-Pinzon M. A., Drew K. L. Neuroprotection: lessons from hibernators, Comp. Biochem. Physiol. 2012. Vol. 162. P. 1–9.

Dhalla N. S., Elmoselhi A. B., Hata T., Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury, Cardiovascular Research. 2000. Vol. 47. P. 446–456.

Didion S. P., Kinzenbaw D. A., Fegan P. E., Didion L. A. et al. Overexpression of CuZn-SOD prevents lipopolysaccharide-induced endothelial dysfunction, Stroke. 2004. Vol. 35. No. 8. P. 1963–1967.

Drew K. L., Buck C. L., Barnes B. M., Christian S. L. et al. Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance, J. Neurochem. 2007. Vol. 102. P. 1713–1726.

Drew K. L., Harris M. B., Lamanna J. C. et al. Hypoxia tolerance in mammalian heterotherms, Am J. Exp. Biol. 2004. Vol. 207. R. 3155–3162.

Drew K. L., Toien O., Rivera P. M., Smith M. A. et al. Role of the antioxidant ascorbate in hibernation and warming from hibernation, Comp. Biochem. Physiol. 2002. Vol. 133. P. 483–492.

Eddy S. F., Storey K. B. p38 MAPK regulation of transcription factor targets in muscle and heart of hibernating bats, Myotis lucifugus, Cell. Biochem. Function. 2007. Vol. 25. P. 759–765.

Elsner R., Oyaseter S., Almaas R., Saugstad O. D. Diving seals, ischemia-reperfusion and oxygen radicals, Comp. Biochem. Physiol. 1998. Vol. 119A. No. 4. P. 975–980.

Geiser F. Metabolic rate and body temperature reduction during hibernation and daily torpor, Annu. Rev. Physiol. 2004. Vol. 66. P. 239–274.

Geiser F., Budinette R. V. The relationship between body mass and rate of rewarming from hibernation and daily torpor in mammals, J. Exp. Biol. 1990. Vol. 151. P. 349–359.

Halliwell B., Gutteridge J. M. C. Free radicals in biology and medicine. 3rd ed. Oxford: Oxford Univ. Press, 1999. 888 p.

Harman D. Free-radical theory of aging. Increasing the functional life span, Ann. N. Y. Acad. Sci. 1994. Vol. 717. P. 1–15.

Heldmaier G., Ortmann S., Elvert R. Natural hypometabolism during hibernation and daily torpor in mammals, Respir. Physiol. Neurobiol. 2004. Vol. 141. P. 317–329.

Hochachka P. W., Somero G. N. Biochemical Adaptation: Mechanism and Process in Physiological Evolution. New York: Oxford University Press, 2002. 466 p.

Hudson N. J., Franklin C. E. Maintaining muscle mass during extended disuse: aestivating frogs as a model species, J. Exp. Biol. 2002. Vol. 205. P. 2297–2303.

Hudson J. W., Scott J. M. Daily torpor in the laboratory mouse, Physiol. Zool. 1979. Vol. 52. No. 2. P. 219–220.

Hulbert A. J., Pamplona R., Buffenstein R. et al. Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals, Physiol. Rev. 2007. Vol. 87. P. 1175–1213.

Hut R. A., Barnes B. M., Daan S. Body temperature patterns before, during, and after semi-natural hibernation in the European ground squirrel, Journal of Comparative Physiology. 2002. Vol. 172B. P. 47–58.

Ilyina T., Baishnikova I., Belkin V., Ruokolaynen T. Vitamins A and E in physiological adaptation of mammals with different ecogenesis, Acta Biol. Univ. Dagavp. 2014. Vol. 14. No. 1. P. 45–50.

James R. S., Staples J. F., Brown J. C. L., Tessier S. T. et al. The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus, The Journal of Experimental Biology. 2013. Vol. 216. P. 2587–2594.

Jaspers P., Kangasjärvi J. Reactive Oxygen Species in Abiotic Stress Signaling, Physiol. Plant. 2010. Vol. 138. P. 405–413.

Kim A. A. Panoramic Overview of Mitochondria and Mitochondrial Redox Biology, Toxicol. Res. Dec. 2014. Vol. 30. No. 4. P. 221–234.

Kooyman G. L., Ponganis P. J. The physiological basis of diving to depth: birds and mammals, Annu. Rev. Physiol. 1998. Vol. 60. P. 19–32.

Ku H. H., Sohal R. S. Comparison of mitochobdrial pro-oxidant generation and anti-oxidant defenses between rat and pigeon: possible basis of variation in longevity and metabolic potential, Mech. Ageing. Dev. 1993. Vol. 72. No. 1. P. 67–76.

Kurtz C. C., Lindell S. L., Mangino M. J., Carey H. V. Hibernation confers resistance to intestinal ischemia-reperfusion injury, Am. J. Physiol. Gastrointest. Liver. Physiol. 2006. Vol. 291. P. 895–901.

Lyman C. P., O’Brien R. C., Greene G. C., Papafrangos E. D. Hibernation and longevity in the Turkish hamster Mesocricetus brandti, Science. 1981. Vol. 212. P. 668–670.

Ma Y. L., Xiongwei Z., Rivera P. M., Toien O. et al. Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels, Am. J. Physiol. Regul. Integr. Comp. Physiol. 2005. Vol. 289. P. 1297–1306.

MacArthur R. A. Aquatic thermoregulation in the muskrat (Ondatra zibethicus): energy demands of swimming and diving, Can. J. Zool. 1984. Vol. 62. P. 241–248.

MacDonald J. A., Storey K. B. Regulation of ground squirrel Na+ K+ -ATPase activity by reversible phosphorylation during hibernation, Biochem. Biophys. Res. Commun. 1999. Vol. 254. P. 424–429.

Maistrovski Y., Biggar K. K., Storey K. B. HIF‐1 alpha regulation in mammalian hibernators: role of non‐coding RNA in HIF‐1 alpha control during torpor in ground squirrels and bats, J. Comp. Physiol. 2012. Vol. 182. P. 849–859.

McCulloch P. F. Animal models for investigating the central control of the mammalian diving response, Front. Physiol. 2012. Vol. 3. P. 1–16.

McMullen D. C., Hallenbeck J. M. Regulation of Akt during torpor in the hibernating ground squirrel, Ictidomys tridecemlineatus, J. Comp. Physiol. 2010. Vol. 180B. No. 6. P. 927–934.

Mongkolsuk S., Helmann J. D. Regulation of inducible peroxide stress responses, Mol. Microbiol. 2002. Vol. 45. P. 9–15.

Morin P., Storey K. B. Antioxidant defense in hibernation: cloning and expression of peroxiredoxins from hibernating ground squirrels, Spermophilus tridecemlineatus, Arch. Biochem. Biophys. 2007. Vol. 461. P. 59–65.

Musacchia X. J., Steffen J. M., Fell R. D. Disuse atrophy of skeletal muscle: animal models, Exerc. Sport Sci. Rev. 1988. Vol. 16. P. 61–87.

Nowell M. M., Choi H., Rourke B. C. Muscle plasticity in hibernating ground squirrels (Spermophilus lateralis) is induced by seasonal, but not lowtemperature, mechanisms, J. Comp. Physiol. 2011. Vol. 181. P. 147–164.

Ohta H., Okamoto I., Hanaya T., Arai S. et al. Enhanced antioxidant defense due to extracellular catalase activity in Syrian hamster during arousal from hibernation, Comp. Biochem. Physiol. 2006. Vol. 143C. P. 484–491.

Okamoto I., Kayano T., Hanaya T., Arai S. et al. Up-regulation of an extracellular superoxide dismutase-like activity in hibernating hamsters subjected to oxidative stress in mid- to late arousal from torpor, Comp. Biochem. Physiol. 2006. Vol. 144C. P. 47–56.

Ozaki Y., Ohashi T., Niwa Y. Oxygen radical production by neutrophils from patients with bacterial infection and rheumatoid arthritis, Inflammation. 1986. Vol. 10. P. 119–130.

Powers S. K., Kavazis A. N., McClung J. M. Oxidative stress and disuse muscle atrophy, J. Appl. Physiol. 2007. Vol. 102. P. 2389–2397.

Prendergast B. J., Freeman D. A., Zucker I. et al. Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels, Am. J. Physiol. Regulatory Integrative Comp. Physiol. 2002. Vol. 282. P. 1054–1062.

Reznik G., Reznik-Schüller H., Emminger A., Mohr U. Comparative studies of blood from hibernating and nonhibernating European hamsters (Cricetus sricetus), Laboratory animal science. 1975. Vol. 25. No. 2. P. 210–215.

Sanz A., Stefanatos R. K. The mitochondrial free radical theory of aging: a critical view, Curr. Aging Sci. 2008. Vol. 1. No. 1. P. 10–21.

Selman C., McLaren J. S., Himanka M. J., Speakman J. R. Effect of long-term cold exposure on antioxidant enzyme activities in a small mammal, Free Radic. Biol. Med. 2000. Vol. 28. P. 1279–1285.

Sohal R. S., Orr W. C. Relationship between antioxidants, prooxidants, and the aging process, Ann. N. Y. Acad. Sci. 1992. Vol. 663. P. 74–84.

Sohal R. S., Ku H. H., Agarwal S. Biochemical correlates of longevity in two closely related rodent species, Biochem. Biophys. Res. Commun. 1993. Vol. 196. P. 7–11.

Shavlakadze T., Grounds M. D. Of bears, frogs, meat, mice and men: insight into the complexity of factors affecting skeletal muscle atrophy/hypertrophy and myogenesis/adipogenesis, Bio Essays. 2006. Vol. 28. No. 10. P. 994–1009.

Storey K. B. Oxidative stress: animal adaptations in nature, Braz. J. Med. Biol. Res. 1996. Vol. 29. P. 1715–1733.

Storey K. B. Metabolic regulation in mammalian hibernation: enzyme and protein adaptations, Comp Biochem Physiol. 1997. Vol. 118. P. 1115–1124.

Storey K. B. Out cold: biochemical regulation of mammalian hibernation – a mini-review, Gerontology. 2010. Vol. 56. P. 220–230.

Storey K. B., Storey J. M. Metabolic rate depression in animals: transcriptional and translational controls, Biol. Rev. Camb. Philos. Soc. 2004. Vol. 79. P. 207–233.

Storey K. B., Storey J. M. Metabolic rate depression: the biochemistry of mammalian hibernation, G. S Makowski (ed.). Advances in clinical chemistry. Elsevier Inc., 2010. P. 77–108.

Stuart J. A., Maddalena L. A., Merilovich M., Robb E. L. A midlife crisis for the mitochondrial free radical theory of aging, Longev. Healthspan. 2014. Vol. 3. P. 4.

Tan D. X., Manchester L. C., Sainz R. M., Mayo J. C. et al. Physiological ischemia/reperfusion phenomena and their relation to endogenous melatonin production: a hypothesis, Endocrine. 2005. Vol. 27. P. 149–158.

Tessier S. N., Storey K. B. Expression of myocyte enhancer factor-2 and downstream genes in ground squirrel skeletal muscle during hibernation, Mol. Cell. Biochem. 2010. Vol. 344. P. 151–162.

Toien O., Drew K. L., Chao M. L. et al. Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels, Am. J. Physiol. Reg. Integr. Comp. Physiol. 2001. Vol. 281. P. 572–583.

Wang L. C. H., Wolowyk M. W. Torpor in mammals and birds, Can. J. Zool. 1988. Vol. 66. P. 133–137.

Wilhelm Filho D., Althoff S. L., Dafre A. L., Boveris A. Antioxidant defenses, longevity and ecophysiology of South American bats, Comparative Biochemistry and Physiology. 2007. Vol. 146C. P. 214–220.

Wilhelm Filho D., González-Flecha B., Bredeston L., Boveris A. Gill diffusion as a physiological mechanism for hydrogen peroxide elimination by fish, Braz. J. Med. Biol. Res. 1994. Vol. 27. P. 2879–2882.

Wilhelm Filho D., Marcon J. L., Fraga C. G., Boveris A. Antioxidant defenses in vertebrates: emphasis on fish and mammals, Trends Comp. Biochem. Physiol. 2000. Vol. 7. P. 33–45.

Wilhelm Filho D., Sell F., Ribeiro L. et al. Comparison between the antioxidant status of terrestrial and diving mammals, Comp. Biochem. Physiol. 2002. Vol. 133. No. 3. P. 885–892.

Wilkinson G. S., South J. M. Life history, ecology and longevity in bats, Aging Cell. 2002. Vol. 1. P. 124–131.

Zenteno-Savín T., Clayton-Hernandez E., Elsner R. Diving seals: are they a model for coping with oxidative stress?, Comp. Biochem. Physiol. 2002. Vol. 133C. No. 4. P. 527–536.

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