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Acute and severe hypobaric hypoxia-induced muscle oxidative stress in mice: the role of glutathione against oxidative damage.

Abstract
This study intended to analyze: (1) the effects of acute and severe hypoxia exposure on skeletal muscle oxidative stress and oxidative damage markers; (2) the protective role of the antioxidant glutathione against oxidative damage; and (3) the expression of heat shock protein 70 kDa (HSP70) induced by this hypoxic insult. Forty mice were divided into four groups: control + placebo (C+P), hypoxia + placebo (H+P), control + l-buthionine-[ S, R]-sulfoximine (BSO, a GSH-depleting compound) (C+BSO) and hypoxia + BSO (H+BSO). Hypoxia groups were continuously exposed for 24 h to a hypobaric hypoxic environment equivalent to an altitude of 7000 m and sacrificed immediately after. Control groups were maintained at sea level during the experimental protocol. Analyzed biochemical parameters were: reduced (GSH) and oxidized (GSSG) glutathione, thiobarbituric acid reactive substances (TBARS), sulfhydryl protein groups (SH), N-acetyl-beta- d-glucosaminidase (NAG) and HSP70 protein. Hypoxia (H+P) per se, compared to C+P, induced a significant increase in %GSSG (5.68 vs. 1.14%), TBARS (436.7 vs. 227.9 nM), NAG (4.49 vs. 3.35 U/mg) and HSP70 (178.7 vs. 100%). Compared with H+P, H+BSO showed a significant decrease in total glutathione (19.30 vs. 6.13 nmol/mg) and an additional increase in %GSSG (5.68 vs. 11.33%) and in HSP70 expression (178.7 vs. 202.2%). However, no further oxidative damage was observed in H+BSO. These data suggest that acute hypoxia per se might enhance oxidative stress; however, the glutathione system seems to have a modest role in skeletal muscle protection against hypoxia-induced oxidative stress. Moreover, hypoxia and BSO treatment is a sufficient stimulus to promote HSP70 overexpression.
AuthorsJosé Magalhães, António Ascensão, José M C Soares, Maria J Neuparth, Rita Ferreira, José Oliveira, Francisco Amado, José A Duarte
JournalEuropean journal of applied physiology (Eur J Appl Physiol) Vol. 91 Issue 2-3 Pg. 185-91 (Mar 2004) ISSN: 1439-6319 [Print] Germany
PMID14557885 (Publication Type: Comparative Study, Evaluation Study, Journal Article)
Chemical References
  • HSP70 Heat-Shock Proteins
  • Buthionine Sulfoximine
  • Glutathione
Topics
  • Acute Disease
  • Altitude
  • Altitude Sickness (classification, metabolism)
  • Animals
  • Ankle Joint (metabolism)
  • Buthionine Sulfoximine (pharmacology)
  • Glutathione (metabolism)
  • HSP70 Heat-Shock Proteins (metabolism)
  • Hypoxia (classification, metabolism)
  • Mice
  • Muscle, Skeletal (drug effects, metabolism)
  • Oxidative Stress
  • Severity of Illness Index

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