Abstract
We tested the hypothesis that hypoxia causes cellular oxidative stress by measuring plasma concentrations of glutathione disulfide (GSSG) in rats exposed to acute and subacute hypoxia. In awake, unanesthetized, catheter-implanted rats, exposure to 8% O2 for 10 min caused pulmonary vasoconstriction and increased plasma GSSG. This increase in plasma GSSG was reversible upon re-exposure to room air. In another group of rats exposed to 48 hours of hypobaric hypoxia (Pb 450 mmHg, equivalent to about 14,500 feet altitude), plasma GSSG, but not total glutathione, was significantly increased over control values (2.83±0.24 vs 1.84±0.14 nmol/ml,p<0.05). While lung tissue GSSG in high altitude-exposed rats were somewhat higher than in controls (17.4±7.0 vs 11.9±3.6 nmol/g wet lung wt.), the difference was not statistically significant. Treatment of the rats with a radical scavenger, DMSO, before altitude exposure, blocked the increase in plasma GSSG (1.86±0.16 nmol/ml). We conclude that both acute and subacute hypoxia increase plasma GSSG in rats and speculate that hypoxia induces cellular oxidative stress in vivo.
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References
Adams JD Jr., Lauterburg BH, Mitchell JR (1983) Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress. J. Pharm. Exp. Ther. 227:749–754.
Adams JD Jr., Lauterburg BH, Mitchell JR (1984) Plasma glutathione disulfide as an index of oxidant stress in vivo: effects of carbon tetrachloride, dimethylnitrosamine, nitrofurantoin, metronidazole, doxorubicin and diquat. Res. Comm. Chem. Path. Pharm. 46:401–410
Akerboom TPM, Bilzer M, Sies H (1982) The relationship of biliary glutathione disulfide efflux and intracellular glutathione disulfide content in perfused rat liver. J. Biol. Chem. 257:4248–4252
Beilke MA, Collins-Lech C, Sohnle PG (1987) Effects of dimethyl sulfoxide on the oxidative function of human neutrophils. J. Lab. Clin. Med. 110:91–96
Berend N (1984) Protective effect of hypoxia on bleomycin lung toxicity in the rat. Am. Rev. Respir. Dis. 130:307–308
Berggren M, Dawson J, Moldeus P (1984) Glutathione biosynthesis in the isolated perfused rat lung: utilization of extracellular glutathione. FEBS Letter. 176:189–192
Block ER, Patel JM (1988) Mechanism of hypoxic injury to pulmonary endothelial cell plasma membranes. Am. Rev. Respir. Dis. 137:325 (Abstract)
Brauer RW, Parrish DE, Way RO, Pratt PC, Pessotti R (1970) Protection by altitude acclimatization against lung damage from exposure to oxygen at 825 mmHg. J. Appl Physiol. 28:474–481
Chang S, Feddersen CO, Henson PM, Voelkel NF (1987) Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats. J. Clin. Invest. 79:1498–1509
Chang S, Lauterberg BH, Voelkel NF (1988) Endotoxin causes neutrophil-independent oxidative stress in rats. J. Appl Physiol. 65:358–367
Cummings SW, Hill KE, Burk RF, Zieglert DM (1986) The effect of hypoxia on release of glutathione by the isolated perfused rat liver. Fed. Proc. 46:216 (Abstract)
Demopoulos HB, Flamm ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol. Scand. (Suppl 492):91–119
Frank L (1982) Protection from O2 toxicity by pre-exposure to hypoxia: lung antioxidant enzyme role. J. Appl. Physiol. 53:457–482
Hultgren JN (1978) High altitude pulmonary edema. In: Staub NC, ed. Lung water and solute exchange. New York: Marcel Dekker, 437–469
Ishikawa T, Sies H (1984) Cardiac transport of glutathione disulfide and S-conjugate. J. Biol. Chem. 259:3838–3843
Jenkinson SG, Spence TH Jr., Lawrence RA, Hill KE, Duncan CA, Johnson KH (1987) Rat lung glutathione release: response to ocidative stress and selenium deficiency. J. Appl. Physiol. 1987; 62:55–60
Joshi UM, Prasada Rao KS, Mehendale HM (1986) Glutathione status in constituted physiological fluid containing bovine serum albumin. Fed. Proc. 45:932 (Abstract)
Kosower NS, Kosower EM (1974) Effect of GSSG on protein synthesis. In: Flohe L, Benohr H, Sies H, Waller HD, Wendel A, eds. Glutathione. Stuttgart: Georg Thieme, 276–286
Misra HP, Fridovich I (1972) The univalent reduction of oxygen by reduced flavins and quinones. J. Biol. Chem. 247:188–192
Rotta A, Canepa A, Hurtado A, Velasquez T, Chavez R (1956) Pulmonary circulation at sea level and at high altitude. J. Appl. Physiol. 9:328–336
Schoene RB, Hackett PH, Henderson WR, Sage EH, Chow M, Roach RC, Mills WJ Jr., Martin TR (1986) High altitude pulmonary edema. Characteristics of lung lavage fluid. J. Am. Med. Assoc. 256:63–69
Sjostrom K, Crapo JD (1983) Structural and biochemical adaptive changes in rat lungs after exposure to hypoxia. Lab Invest. 48:68–79
Srivastava SK, Beutler E (1969) The transport of oxidized glutathione from human erythrocytes. J. Biol. Chem. 244:9–16
Stelzner TJ, Chang S, Voelkel NF, Weil JV (1987) DMSO prevents increases in pulmonary transvascular protein escape and plasma GSSG in hypoxia. Am. Rev. Respir. Dis. 135:A264 (Abstract)
Stelzner TJ, O’Brien RF, Sato K, Weil JV (1988) Hypoxia-induced increases in pulmonary transvascular protein escape in rats: Modulation by glucocorticoids. J. Clin. Invest. 82:1840–1847
Tietze F (1969) Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal. Biochem. 27:502–522
White CW, Mimmack RF, Repine JE (1986) Accumulation of lung tissue oxidized glutathione (GSSG) as a marker of oxidant-induced lung injury. Chest 89:111S-113S
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Chang, SW., Stelzner, T.J., Weil, J.V. et al. Hypoxia increases plasma glutathione disulfide in rats. Lung 167, 269–276 (1989). https://doi.org/10.1007/BF02714956
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DOI: https://doi.org/10.1007/BF02714956