Li Y, Yousef I M, Plaa G L
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Liver. 1995 Oct;15(5):271-5. doi: 10.1111/j.1600-0676.1995.tb00684.x.
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.
研究了异硫氰酸1-萘酯生物活化的重要性。给大鼠注射异硫氰酸1-萘酯40分钟后，在2.5小时内收集胆汁；然后切除肝脏并匀浆。使用气相色谱-质谱联用仪对大鼠胆汁和肝脏中的异硫氰酸1-萘酯及其代谢产物进行鉴定和定量。在所有接受异硫氰酸1-萘酯处理的动物中均发现了三种主要化合物。它们被鉴定为异氰酸1-萘酯、1-萘胺和母体化合物异硫氰酸1-萘酯。当在注射异硫氰酸1-萘酯（300mg/kg）前30分钟给大鼠注射放线菌酮（可减轻异硫氰酸1-萘酯的毒性）时，异氰酸1-萘酯的浓度显著低于仅接受异硫氰酸1-萘酯的大鼠。放线菌酮也抑制了1-萘胺的出现，尽管程度不如异氰酸1-萘酯。另一方面，苯巴比妥可增强异硫氰酸1-萘酯的肝毒性，它会增加异氰酸1-萘酯和1-萘胺的形成。提示异氰酸1-萘酯、1-萘胺以及异硫氰酸1-萘酯释放的高反应性硫可能参与了异硫氰酸1-萘酯的肝毒性作用。
