Effect of glutathione status on covalent binding and pneumotoxicity of 3-methylindole in goats.
A study was conducted to investigate the relationship between glutathione (GSH) status, in-vivo metabolite covalent binding and 3-methylindole (3MI)-induced lung injury in goats. Cysteine or diethylmaleate pretreatments were given to sustain or deplete GSH, respectively, prior to intravenous 14C-3MI administration. Cysteine pretreatment prolonged survival times, decreased (P less than .05) covalent lung injury. Diethylmaleate pretreatment shortened survival times, increased (P less than .05) covalent binding and enhanced lung injury. Covalent binding was higher (P less than .05) in lung compared to liver and kidney. 3-Methylindole alone depleted GSH in 4 hours to 36, 66, and 75% of controls in these tissues, respectively. The relationship between tissue GSH, covalent binding and toxicity supports the hypothesis that 3MI-induced pneumotoxicity results from the formation of activated intermediates and that GSH plays a role in detoxication of these 3MI metabolites.
D000818:Animals; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006041:Goats; D007211:Indoles / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008298:Maleates / Q000494:pharmacology; D012862:Skatole / Q000378:metabolism / Q000633:toxicity*
D007211:Indoles; D008298:Maleates; D012862:Skatole; C014476:diethyl maleate; D005978:Glutathione; D003545:Cysteine