Potentiation of oxygen toxicity in rats by dietary protein or amino acid deficiency

Abstract

Rats fed 3% casein diets for 6 days showed an increased susceptibility to greater than 98% oxygen [mean survival time 46.9 +/- 4.1 (SD) h] compared with animals fed 25% casein diets (mean survival time 60 +/- 5 h). The 3% casein diet did not reduce the responses to hyperoxia of lung glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase (NAD(P)H), which maintain tissue levels of reduced glutathione or lung superoxide dismutase levels. While supplementation of the 3% casein diet with the sulfur-containing amino acids (cysteine, cystine, or methionine) prevented the increased oxygen toxicity, supplementation with leucine, a nonsulfur-containing amino acid, had no effect on potentiation of toxicity. Animals fed the unsupplemented 3% casein diet failed to show an elevation of lung glutathione in response to hyperoxia. When the 3% casein diet was supplemented with cysteine, total lung glutathione levels increased normally during oxygen exposure. Supplementation of the 25% protein diet with cysteine did not further protect these animals. We conclude that potentiation of oxygen toxicity by dietary protein deficiency in the rat is due to the low sulfur-containing amino acid content of the diet; the mechanism of increased toxicity by hyperoxia is probably related to an inability to increase glutathione levels due to a shortage of the cysteine component of the glutathione tripeptide.

Effects of Fasting on Tissue Contents of Coenzyme A and Related Intermediates in Rats

“…Although decreases in lung contents of GSH in animals exposed to hyperoxia have not been observed in most studies reported to date (21,22,28,38,39), fasting or limiting dietary protein intake can potentiate or accelerate the emergence of lung damage in animals exposed to hyperoxia (21, 39 -41). The increase in animal sensitivity to normobaric hyperoxia was paralleled by attenuation or prevention of the increases in lung GSH levels usually observed in animals fed normal diets after 24 to 48 h of normobaric hyperoxia.…”

“…The increase in animal sensitivity to normobaric hyperoxia was paralleled by attenuation or prevention of the increases in lung GSH levels usually observed in animals fed normal diets after 24 to 48 h of normobaric hyperoxia. Deneke and coworkers (21,23) reported that normal resistance to hyperoxia and increases in lung GSH levels could be restored in proteinrestricted animals by supplementation of protein-deficient diets with cysteine, cystine, or methionine, but not by comparable supplementation with leucine. The apparent contradictions suggested by the effects of protein deprivation and amino acid supplementation with the absence of primary effects of hyperoxia on lung GSH levels thus suggested either that responses of hyperoxic lung injury to divalent sulfur availability were mediated by compartmental or cell type-specific effects on lung GSH or on extrapulmonary GSH pools, or that the pathophysiologic effects of protein deprivation on the responses to hyperoxia were influenced by effects on species other than GSH.…”

“…Deneke and coworkers (21)(22)(23) showed that a low-protein diet exacerbated oxygen toxicity, but cysteine supplementation of the same low-protein diets returned susceptibility to hyperoxia to normal, whereas equimolar amounts of leucine were without effect. Deneke et al (21)(22)(23) concluded that exacerbation of hyperoxia lung injury was caused by insufficient supplies of cysteine or methionine, leading to an inability to increase GSH levels during hyperoxia. Stabler and coworkers (33) recently found that very premature baboons may have decreased cysteine availability or increased cysteine utilization, similar to the abnormalities previously shown in both preterm and term human infants in respiratory distress (34).…”

Oxidative stress and regulation of glutathione in lung inflammation

“…Treatment with reducing agents such as NAC or GSH increases intracellular GSH levels by making intracellular cysteine available and reducing cystine to cysteine in bovine pulmonary artery endothelial cells [121]. Furthermore, NAC increases intracellular GSH levels in bovine pulmonary artery endothelial cells even in the absence of cystine in the medium [135].…”

Biochemical Manifestations of Oxygen Toxicity in the Newborn Lamb

“…The effects of GSH depletion on the ability of the lung to withstand an oxidant stress are not clear. Deneke et al (29) found that rats fed a diet deficient in sulfur-containing amino acids were more susceptible to oxygen-induced lung injury. Furthermore, although lung GSH content increased with duration of oxygen exposure in rats fed a normal protein diet or one supplemented with cysteine, GSH content decreased during the hyperoxic exposure of rats fed a diet deficient in sulfur-containing amino acids.…”