The effect of lung concentrations of glutathione and vitamin E on the pulmonary toxicity of 3-methylindole.
The relative roles of tissue glutathione and vitamin E concentrations in the pneumotoxicity of 3-methylindole were studied. Thirty-two goats were divided into four groups and pretreated with (i) vitamin E + cysteine, (ii) vitamin E + diethylmaleate, (iii) cysteine, and (iv) diethylmaleate to vary tissue concentrations of glutathione and (or) vitamin E. Lung tissue concentrations of glutathione, vitamin E, and cytochrome P-450 were measured after pretreatments in four of eight animals in each group. Groups pretreated with cysteine had higher glutathione levels in the lung than those of diethylmaleate-pretreated goats. Goats receiving vitamin E had significantly higher concentrations of vitamin E than unsupplemented groups. After pretreatments the other four goats in each group were challenged with 3-methylindole (0.03 g/kg body weight) by intrajugular infusion. The severity of lung lesions was evaluated and scored by gross and microscopic examination at 72 h after infusion. 3-Methylindole-induced lung lesions were severe when tissue glutathione was reduced and were mild when tissue glutathione was induced. Enhancement of tissue vitamin E did not significantly affect 3-methylindole toxicity. These results indicate that the initial toxicological event is likely to be the result of binding of 3-methylindole free radical covalently to cellular protein rather than lipid peroxidation.
Kubow
S
S
Department of Nutritional Sciences, College of Biological Science, University of Guelph, Ont., Canada.
Bray
T M
TM
D000818:Animals; D003545:Cysteine / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D006041:Goats; D007211:Indoles / Q000633:toxicity*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008298:Maleates / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D012862:Skatole / Q000633:toxicity*; D014810:Vitamin E / Q000378:metabolism* / Q000633:toxicity
D007211:Indoles; D008298:Maleates; D014810:Vitamin E; D012862:Skatole; C014476:diethyl maleate; D005978:Glutathione; D003545:Cysteine