α-Naphthylisothiocyanate (ANIT)-induced hepatotoxicity and disposition in various species

Abstract

Species difference to ANIT-induced hepatotoxicity was confirmed by measurement of plasma bilirubin, BSP retention, and bile flow in rats, mice, guinea pigs, hamsters, and rabbits following ANIT administration. Rats and mice showed significant hyperbilirubinemia, BSP retention, and bile stasis following ANIT treatment. Contrary to previous reports, the guinea pig developed significant elevation of plasma bilirubin, BSP retention, and bile stasis following acute ANIT treatment. The hamster, not previously studied, was comparatively insensitive to ANIT-induced hyperbilirubinemia, BSP retention or bile stasis. The rabbit failed to develop hyperbilirubinemia, BSP retention, or bile stasis even with toxic doses of ANIT. Evaluation of urinary 14C metabolites from the various species by thin-layer chromatography showed definite qualitative and quantitative differences in the hamster and rabbit compared with the remaining species. ANIT- 14C was not found to be present in any of the species urine. The results of these experiments suggest that ANIT hepatotoxicity is related to its metabolism. The metabolism may involve either specific enzymatic biotransformation pathways which are variable among the different species or may be related to the binding of ANIT to specific substances such as a protein which are variable among the various species in their composition and/or contribution to normal biliary excretion.