1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate.
The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
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Yousef
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Plaa
D015057:1-Naphthylamine / Q000378:metabolism*; D015058:1-Naphthylisothiocyanate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001711:Biotransformation; D003513:Cycloheximide / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015058:1-Naphthylisothiocyanate; D015057:1-Naphthylamine; D003513:Cycloheximide; D010634:Phenobarbital