Bile secretion and liver microsomal mixed function oxidase system in mice with griseofulvin-induced hepatic protoporphyria

Administration of 2.5% griseofulvin in the diet to male CD 1 mice produced protoporphyria and cholestasis. Protoporphyria became evident as early as after 10 days of treatment, whereas cholestasis, expressed in terms of total bile flow reduction, developed only after 45 days of griseofulvin. Bile flow impairment was due both to the length of treatment and to the severity of liver protoporphyria. Griseofulvin administration was also associated with a significant modification of the relative amounts of hepatic microsomal cytochromes P-450 and b 5, a loss in concentration/mg of protein of cytochrome P-450 and a concomitant increase of b 5. Despite these changes, the activity of aniline hydroxylase expressed per mg of microsomal protein, assessed in vitro, was not modified.