Protein deficiency potentiates oxygen toxicity.

Male rats (Charles River COBS-CD derived) fed protein-deficient diets showed enhanced toxicity with failure of elevation of lung glutathione levels with exposure to greater than 98% O2. Replenishment of S-containing amino acids in the protein-deficient diets allowed elevation of lung glutathione and prevention of enhanced toxicity. Studies with endothelial cell cultures exposed to hyperoxia showed elevation of cellular glutathione coupled with enhanced uptake of amino acid precursors of glutathione. We postulate that hyperoxia causes an enhancement of uptake of S-containing amino acids necessary for glutathione synthesis, overriding glutathione feedback of its own synthesis. Limitation of available S-containing amino acids prevents elevation of glutathione synthesis and is detrimental to the cell exposed to hyperoxia.