title: 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.
authors.affiliation: Department of Sport Biology, Faculty of Sport Sciences, University of Porto, Rua Dr. Plácido Costa 91, 4200-450, Porto, Portugal. jmaga@fcdef.up.pt
authors.forename: José
authors.initials: J
authors.lastname: Magalhães
authors.forename: António
authors.initials: A
authors.lastname: Ascensão
authors.forename: José M C
authors.initials: JM
authors.lastname: Soares
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Neuparth
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.forename: José
authors.initials: J
authors.lastname: Oliveira
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
authors.forename: José A
authors.initials: JA
authors.lastname: Duarte
mesh_terms: D000208:Acute Disease; D000531:Altitude; D000532:Altitude Sickness / Q000145:classification / Q000378:metabolism*; D000818:Animals; D000843:Ankle Joint / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000860:Hypoxia / Q000145:classification / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D012720:Severity of Illness Index
chemical_list: D018840:HSP70 Heat-Shock Proteins; D019328:Buthionine Sulfoximine; D005978:Glutathione