Roles of selenium and sulfur-containing amino acids in protection against oxygen toxicity.

Tolerance and adaptation to hyperoxia have been correlated with increases in antioxidant enzymes. This study evaluated whether selenium deficiency would prevent an increase in glutathione peroxidase (GSHPX), a selenium-containing enzyme, during oxygen exposure, and, thus, inhibit adaptation. Because the Torula yeast-based diet, which was used to produce selenium deficiency, was also deficient in cysteine and methionine, the effects of these deficiencies were also evaluated. When rats were exposed to 80% oxygen for 1 week, mortality was 80% for rats deficient in both selenium and the sulfur-containing amino acids, 40% for selenium-deficient rats, 35% for cysteine- and methionine-deficient rats, and 0% for rats fed either a standard laboratory diet or a selenium, cysteine-, and methionine-supplemented Torula yeast diet. However, only one of the six surviving rats with low selenium and none of the rats from any other dietary group died during a subsequent 96 hours of 98% oxygen, indicating adaptation to hyperoxia (LD50 for unadapted rats is 72 hours.) GSHPX activity (per gram of dry weight) was decreased 85% in lungs from unexposed rats fed the low selenium diets. After oxygen exposure, lung GSHPX activity was elevated in all dietary groups. Rats fed the high selenium diets had a 47% increase in enzyme activity, whereas rats with high selenium had a 214% increase. Although hyperoxia caused a relatively high percentage increase in the low Se rats, the resulting absolute GSHPX activity was only 34 to 70% of that of unexposed high selenium rats. The results indicate that both selenium and sulfur-containing amino acids contribute to antioxidant defense. However, although the stress of hyperoxic exposure produces an increase in glutathione peroxidase activity, the absolute lung GSHPX activity is better correlated with tolerance than with adaptation to hyperoxia.