Effect of thiocarbonyl compounds on alpha-naphthylisothiocyanate-induced hepatotoxicity and the urinary excretion of [35S]alpha-naphthylisothiocyanate in the rat.
The effect of disulfiram (DSF), sodium diethyldithiocarbamate (DDTC), methyl diethyldithiocarbamate (Me-DDTC), and ethionamide on the hepatotoxic response of alpha-naphthylisothiocyanate (ANIT) was studied in the rat. The hyperbilirubinemic response of ANIT was significantly inhibited by ip or po DSF pretreatment. A more marked inhibition of toxicity occurred when DSF was given via ip injection. DDTC, Me-DDTC, and ethionamide significantly inhibited ANIT-induced hyperbilirubinemia. Me-DDTC is approximately three times more potent than DDTC as an inhibitor of toxicity. Approximately 16% of a dose of [35S]ANIT was excreted in the urine as inorganic sulfate 48 hr after dosing. Me-DDTC administered simultaneously with [35S]ANIT significantly reduced urinary [35S]sulfate excretion in the first 24 hr. Ethionamide reduced urinary [35S]sulfate excretion. Pretreatment with phenobarbital which stimulates toxicity in vivo increased urinary [35S]sulfate excretion 300% in the first 12 hr. Thus, this study shows that agents which sensitize or protect rats from the toxic effects of ANIT, correspondingly stimulate or inhibit the oxidative desulfuration of [35S]ANIT in vivo.
D015058:1-Naphthylisothiocyanate / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004221:Disulfiram / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D005000:Ethionamide / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000652:urine; D013859:Thiocarbamates / Q000494:pharmacology*; D013861:Thiocyanates / Q000633:toxicity*
D013431:Sulfates; D013859:Thiocarbamates; D013861:Thiocyanates; D015058:1-Naphthylisothiocyanate; D004050:Ditiocarb; D005000:Ethionamide; D004221:Disulfiram