The nature of α-naphthylisothiocyanate-induced cholestasis

Abstract

Cholestasis was established in mice by the administration of a single oral dosage of 150 mg of α-naphthylisothiocyanate per kilogram and compared to extrahepatic cholestasis effected by surgical occlusion of the common bile duct. Plasma levels of conjugated and unconjugated bilirubin, and of intravenously injected sulfobromophthalein and its metabolic product, were measured as indicators of the functional integrity of the liver of the two preparations. Equal degrees of hyperbilirubinemia and sulfobromophthalein retention were achieved by the two treatments. However, the plasma of α-naphthylisothiocyanate-treated mice contained increased levels of the metabolic products of bilirubin and sulfobromophthalein. The unconjugated form of bilirubin was elevated in animals with surgically occluded bile ducts. The onset of hyperbilirubinemia and bilirubinuria was more rapid following the drug treatment. Therefore, α-naphthylisothiocyanate-induced cholestasis differs from extrahepatic cholestasis in the following ways: (1) the onset of stasis as judged by the appearance of hyperbilirubinemia is more rapid; (2) the increase in plasma bilirubin represents an increase solely in conjugated bilirubin; (3) a higher proportion of intravenously injected sulfobromophthalein appears in the altered form; and (4) plasma levels of intravenously injected sulfobromophthalein decrease more rapidly.