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

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.

Cellular distribution of Hsp70 expression in rat skeletal muscles. Effects of moderate exercise training and chronic hypoxia

“…Our data further show that this occurred in the posterior hindlimb muscles, which play a dynamic role during running, whereas it was apparently absent in muscles, like the tibialis anterior, which exhibited a predominant tonic activity (Jasmin and Gisiger 1990). In addition, normobaric hypoxia significantly increased muscle levels of Hsp70, similarly to that described after exposure to chronic hypobaric hypoxia (Magalhaes et al 2005a). Nevertheless, the extent of the Hsp70 response to either sustained or intermittent hypoxia was strikingly different, insofar chronic exposure to normobaric hypoxia induced a threefold increase in Hsp70 protein levels, whereas the intermittent one only a 50% increase.…”

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“…Data from Magalhães and co-workers in humans and rats, both in plasma (69,73) and skeletal muscle (70)(71)(72) , are consistent with others reporting increased oxidative damage and an inability of the antioxidant system to cope with the increased production of RONS under hypoxia (7,23,52,54,66,77,89,98,106) . Increased lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS) or malondialdehyde (MDA), and enhanced protein oxidation estimated by carbonyl derivatives groups or sulfhydryl groups (SH) were found at distinct levels of cell organization (69)(70)(71)(72)(73) . Moreover, DNA damage expressed as increased strand breaks and endonuclease III-sensitive sites was described in human skeletal muscle after 2 weeks of hypoxia (107) .…”

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

“…Under hypoxic conditions, muscle mass in animals (343) [347]). In COPD, hypoxia is a likely factor driving changes in limb muscle tissue (200) 349).…”