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Int J Sports Med 2005; 26(2): 102-109
DOI: 10.1055/s-2004-817858
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Acute and Chronic Exposition of Mice to Severe Hypoxia: The Role of Acclimatization against Skeletal Muscle Oxidative Stress

J. Magalhães1 , A. Ascensão1 , J. M. C. Soares1 , R. Ferreira1 , M. J. Neuparth2 , J. Oliveira1 , F. Amado2 , F. Marques3 , J. A. Duarte1
  • 1Department of Sport Biology, Faculty of Sport Science, University of Porto, Porto, Portugal
  • 2Department of Chemistry, University of Aveiro, Aveiro, Portugal
  • 3Department of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal
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Publikationsverlauf

Accepted after revision: January 12, 2004

Publikationsdatum:
30. Juli 2004 (online)

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Abstract

The role of acclimatization and the effect of persistent severe hypoxia (7000 m) were analyzed in mice soleus muscle with respect to oxidative stress (glutathione redox status) and damage markers (TBARS and SH protein groups), NAG and SOD activities and HSP70 expression. Forty mice were divided into one normobaric-normoxic control group and four hypobaric-hypoxic experimental groups (n = 8). One experimental group (1 D) was acutely exposed to a simulated altitude of 7000 m in a hypobaric chamber for 1 day. Another experimental group (ACCL + 1 D) was exposed to a 3 days acclimatization period plus 1 day of hypoxia exposure at 7000 m. The third experimental group (ACCL + 8 D) was exposed to the same acclimatization protocol, remaining 8 subsequent days at 7000 m. The fourth experimental group (8 D) was chronically exposed without acclimatization. ACCL + 1 D showed a significant decrease (p < 0.05) in oxidative stress and damage compared to the 1 D group. Concerning chronic severe hypoxia, acclimatization was truly vital, since 8 D animals died after 5 days of exposure. Oxidative stress and damage markers in ACCL + 8 D tended to gradually increase throughout the 8 days of the hypoxic period. Total SOD activity did not change in 1 D compared to control; however, it increased significantly (p < 0.05) in ACCL + 1 D and ACCL + 8 D. HSP70 expression followed the observed oxidative stress and damage pattern, suggesting a protective role against hypoxia-induced oxidative stress. The present study supports the hypothesis that acclimatization attenuates oxidative stress and damage induced by acute hypoxia, although a trend to a gradually increased oxidative deleterious effect in skeletal muscle seems to occur during persistent severe hypoxia even after a previous acclimatization period.

Key words

Altitude - acclimatization - oxidative stress - oxidative damage - skeletal muscle - HSP70 expression

References

  • 1 Askew E W. Work at high altitude and oxidative stress: antioxidant nutrients.  Toxicology. 2002;  180 107-119
    CrossrefPubMedSuche in Google Scholar
  • 2 Bailey D, Davies B, Davison G, Young I. Oxidatively stressed out at high-altitude!.  Intern Soc Mountain Med Newsletter. 2000;  10 3-13
    PubMedSuche in Google Scholar
  • 3 Bailey D M, Davies B, Young I S. Intermittent hypoxic training: implications for lipid peroxidation induced by acute normoxic exercise in active men.  Clin Sci (Lond). 2001;  101 465-475
    CrossrefPubMedSuche in Google Scholar
  • 4 Beauchamp C, Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels.  Anal Biochem. 1971;  44 276-287
    CrossrefPubMedSuche in Google Scholar
  • 5 Benjamin I J, Kroger B, Williams R S. Activation of the heat shock transcription factor by hypoxia in mammalian cells.  Proc Natl Acad Sci USA. 1990;  87 6263-6267
    PubMedSuche in Google Scholar
  • 6 Bertholf R L, Nicholson J R, Wills M R, Savory J. Measurement of lipid peroxidation products in rabbit brain and organs (response to aluminum exposure).  Ann Clin Lab Sci. 1987;  17 418-423
    PubMedSuche in Google Scholar
  • 7 Cerretelli P, Hoppeler H. Morphologic and metabolic response to chronic hypoxia: The muscle system. Fregly M, Blatteis C Handbook of Physiology. Section 4: Environmental Physiology. New York; Oxford University Press 1996: 1155-1182
    Suche in Google Scholar
  • 8 Droge W. Free radicals in the physiological control of cell function.  Physiol Rev. 2002;  82 47-95
    CrossrefPubMedSuche in Google Scholar
  • 9 Duranteau J, Chandel N S, Kulisz A, Shao Z, Schumacker P T. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes.  J Biol Chem. 1998;  273 11619-11624
    CrossrefPubMedSuche in Google Scholar
  • 10 Halliwell B, Gutteridge J M. Free Radicals in Biology and Medicine. Oxford; Clarendon Press 1999
    Suche in Google Scholar
  • 11 Heinicke K, Prommer N, Cajigal J, Viola T, Behn C, Schmidt W. Long-term exposure to intermittent hypoxia results in increased hemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels in man.  Eur J Appl Physiol. 2003;  88 535-543
    CrossrefPubMedSuche in Google Scholar
  • 12 Hollander J, Fiebig R, Gore M, Ookawara T, Ohno H, Ji L L. Superoxide dismutase gene expression is activated by a single bout of exercise in rat skeletal muscle.  Pflugers Arch. 2001;  442 426-434
    PubMedSuche in Google Scholar
  • 13 Hoshikawa Y, Ono S, Suzuki S, Tanita T, Chida M, Song C, Noda M, Tabata T, Voelkel N F, Fujimura S. Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia.  J Appl Physiol. 2001;  90 1299-1306
    PubMedSuche in Google Scholar
  • 14 Hu M-L. Measurement of protein thiol groups and GSH in plasma. Parker L Methods in Enzymology. San Diego; Academic Press 1990: 380-385
    Suche in Google Scholar
  • 15 Ji L L, Leeuwenburgh C. Glutathione and exercise. Somani S Pharmacology in Exercise and Sports. Boca Raton, Florida; CRC Press 1996: 97-123
    Suche in Google Scholar
  • 16 Joanny P, Steinberg J, Robach P, Richalet J P, Gortan C, Gardette B, Jammes Y. Operation Everest III (Comex '97): the effect of simulated severe hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise.  Resuscitation. 2001;  49 307-314
    CrossrefPubMedSuche in Google Scholar
  • 17 Kehrer J P, Lund L G. Cellular reducing equivalents and oxidative stress.  Free Radic Biol Med. 1994;  17 65-75
    CrossrefPubMedSuche in Google Scholar
  • 18 Kohin S, Stary C M, Howlett R A, Hogan M C. Preconditioning improves function and recovery of single muscle fibers during severe hypoxia and reoxygenation.  Am J Physiol. 2001;  281 C142-146
    PubMedSuche in Google Scholar
  • 19 Kulisz A, Chen N, Chandel N S, Shao Z, Schumacker P T. Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in cardiomyocytes.  Am J Physiol. 2002;  282 L1324-1329
    PubMedSuche in Google Scholar
  • 20 Laclau M N, Boudina S, Thambo J B, Tariosse L, Gouverneur G, Bonoron-Adele S, Saks V A, Garlid K D, Dos Santos P. Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase.  J Mol Cell Cardiol. 2001;  33 947-956
    CrossrefPubMedSuche in Google Scholar
  • 21 Laemmli U K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.  Nature. 1970;  227 680-685
    PubMedSuche in Google Scholar
  • 22 Leeuwenburgh C, Ji L L. Alteration of glutathione and antioxidant status with exercise in unfed and refed rats.  J Nutr. 1996;  126 1833-1843
    PubMedSuche in Google Scholar
  • 23 Locke M, Noble E G, Atkinson B G. Exercising mammals synthesize stress proteins.  Am J Physiol. 1990;  258 C723-729
    PubMedSuche in Google Scholar
  • 24 Lowry O H, Rosenbrough N, Farr A L, Radall R J. Protein measurement with the folin phenol reagent.  J Biol Chem. 1951;  193 265-275
    PubMedSuche in Google Scholar
  • 25 Norese M F, Lezon C E, Alippi R M, Martinez M P, Conti M I, Bozzini C E. Failure of polycythemia-induced increase in arterial oxygen content to suppress the anorexic effect of simulated high altitude in the adult rat.  High Alt Med Biol. 2002;  3 49-57
    PubMedSuche in Google Scholar
  • 26 Pfeiffer J M, Askew E W, Roberts D E, Wood S M, Benson J E, Johnson S C, Freedman M S. Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training.  Wilderness Environ Med. 1999;  10 66-74
    PubMedSuche in Google Scholar
  • 27 Powers S K, Ji L L, Leeuwenburgh C. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review.  Med Sci Sports Exerc. 1999;  31 987-997
    CrossrefPubMedSuche in Google Scholar
  • 28 Powers S K, Locke, Demirel H A. Exercise, heat shock proteins, and myocardial protection from I-R injury.  Med Sci Sports Exerc. 2001;  33 386-392
    PubMedSuche in Google Scholar
  • 29 Radak Z, Lee K, Choi W, Sunoo S, Kizaki T, Oh-ishi S, Suzuli K, Tanig. Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats. Eur J.  Appl Physiol. 1994;  69 392-395
    PubMedSuche in Google Scholar
  • 30 Salminen A. Lysosomal changes in skeletal muscles during the repair of exercise injuries in muscle fibers.  Acta Physiol Scand Suppl. 1985;  539 1-31
    PubMedSuche in Google Scholar
  • 31 Sarada S K, Dipti P, Anju B, Pauline T, Kain A K, Sairam M, Sharma S K, Ilavazhagan G, Kumar D, Selvamurthy W. Antioxidant effect of beta-carotene on hypoxia induced oxidative stress in male albino rats.  J Ethnopharmacol. 2002;  79 149-153
    CrossrefPubMedSuche in Google Scholar
  • 32 Schoene R B, Roach R C, Hackett P H, Sutton J R, Cymerman A, Houston C S. Operation Everest II: ventilatory adaptation during gradual decompression to extreme altitude.  Med Sci Sports Exerc. 1990;  22 804-810
    PubMedSuche in Google Scholar
  • 33 Sen C K, Atalay M, Hanninen O. Exercise-induced oxidative stress: glutathione supplementation and deficiency.  J Appl Physiol. 1994;  77 2177-2187
    PubMedSuche in Google Scholar
  • 34 Simon-Schnass I. Risk of oxidative stress during exercise at high altitude. Sen CK, Packer L, Hannienen O Handbook of Oxidants and Antioxidants in Exercise. Amsterdam; Elsevier 2000: 191-210
    Suche in Google Scholar
  • 35 Singh S N, Vats P, Kumria M M, Ranganathan S, Shyam R, Arora M P, Jain C L, Sridharan K. Effect of high altitude (7620 m) exposure on glutathione and related metabolism in rats.  Eur J Appl Physiol. 2001;  84 233-237
    PubMedSuche in Google Scholar
  • 36 Thomason D, Menon V. HSPs and protein synthesis in striated muscle. Locke M, Noble E Exercise and Stress Response - the Role of Stress Proteins. Boca Raton, Florida; CRC Press 2002: 79-96
    Suche in Google Scholar
  • 37 Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues.  Anal Biochem. 1969;  27 502-522
    CrossrefPubMedSuche in Google Scholar
  • 38 Vanden Hoek T L, Becker L B, Shao Z, Li C, Schumacker P T. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes.  J Biol Chem. 1998;  273 18092-18098
    CrossrefPubMedSuche in Google Scholar
  • 39 Vats P, Mukherjee A K, Kumria M M, Singh S N, Patil S K, Rangnathan S, Sridharan K. Changes in the activity levels of glutamine synthetase, glutaminase and glycogen synthetase in rats subjected to hypoxic stress.  Int J Biometeorol. 1999;  42 205-209
    CrossrefPubMedSuche in Google Scholar
  • 40 Wen H C, Lee C C, Lee W C, Huang K S, Lin M T. Chronic hypoxia preconditioning increases survival in rats suffering from heatstroke.  Clin Exp Pharmacol Physiol. 2002;  29 435-440
    CrossrefPubMedSuche in Google Scholar
  • 41 West J B. Acclimatization and tolerance to extreme altitude.  J Wilderness Med. 1993;  4 17-26
    PubMedSuche in Google Scholar
  • 42 West J B. Physiology of extreme altitude. Fregly M, Blatteis C Handbook of Physiology. Section 4: Environmental Physiology. New York; Oxford University Press 1996: 1307-1325
    Suche in Google Scholar
  • 43 Westerterp-Plantenga M S, Westerterp K R, Rubbens M, Verwegen C R, Richelet J P, Gardette B. Appetite at “high altitude” [Operation Everest III (Comex ‘97)]: a simulated ascent of Mount Everest.  J Appl Physiol. 1999;  87 391-399
    CrossrefPubMedSuche in Google Scholar
  • 44 Wood J G, Johnson J S, Mattioli L F, Gonzalez N C. Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation.  J Appl Physiol. 1999;  87 1734-1740
    PubMedSuche in Google Scholar
  • 45 Wood J G, Mattioli L F, Gonzalez N C. Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats.  J Appl Physiol. 1999;  87 873-881
    PubMedSuche in Google Scholar
  • 46 Zhong N, Zhang Y, Fang Q Z, Zhou Z N. Intermittent hypoxia exposure-induced heat-shock protein 70 expression increases resistance of rat heart to ischemic injury.  Acta Pharmacol Sin. 2000;  21 467-472
    PubMedSuche in Google Scholar

Dr. José Magalhães

Department of Sport Biology · Faculty of Sport Sciences · University of Porto

Rua Dr. Plácido Costa, 91

4200-450 Porto

Portugal

Telefon: + 351225074774

Fax: + 35 12 25 50 06 89

eMail: jmaga@fcdef.up.pt