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

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.

Ototoxic Interactions of Ethacrynic Acid and Streptomycin

Various aminoglycoside antibiotics and potent diuretics are known to depress cochlear and vestibular function. Several clinical and research studies suggest that the drugs administered together produce enhanced ototoxicity. The present series of experiments determines the depressive effects of ethacrynic acid and streptomycin, alone or in combination, upon the vestibular system of the cat. The changes in function, when quantified, indicate an addition, rather than a potentiation of toxicity, and suggest different sites of action.

Potentiation of toxicity of Sumithion by phosphamidon in the rat

Acute oral dosing of male rats with mixtures of Sumithion and phosphamidon produces a marked potentiation of toxicity as evidenced by increased mortality. While potentiation also occurs with female rats dosed with mixtures containing relatively low concentrations of Sumithion, the effect diminishes as the Sumithion concentration is increased. It is concluded that this potentiation is associated with a nonlinear thiophosphate conversion reaction.