Abstract
In this study, the analysis of the mechanism of alpha-naphthylisothiocyanate (ANIT) induced cholestasis was attempted by the examination of cytochrome P-450 (P-450) levels in liver microsome and nucleus using phenobarbital and cycloheximide. From the result of this examination, following hypothesis might be proposed. ANIT might be metabolized and turned to a hepatotoxic compound in the liver microsome, these chemically active ANIT might disturbe the bile canalicular portion and bile epithelium. Pretreatment of phenobarbital enhances P-450 production in the microsome. Therefore, the large amount of P-450 metabolizes a correspondingly large amount of ANIT to chemically active materials which resulted in progressive cholestasis. On the other hand, cycloheximide inhibits the production of microsomal P-450 which is closely related to the appearance of cholestasis with ANIT.
This study clarified in part the mechanism of ANIT induced cholestasis and the relationship, such as a precursor-product, between nuclear P-450 and microsomal P-450 was suspected.
