Cholic acid amelioration of light and electron microscopic hepatic lesions in experimental protoporphyria

We studied the effects of cholic acid treatment on hepatic histology and ultrastructure in mice with griseofulvin-induced protoporphyria. After 5 weeks of feeding griseofulvin alone, control mice developed darkly pigmented livers which by light microscopy showed birefringent, brown pigment deposits in bile ducts and ductules, sinusoidal Kupffer cell aggregates, and occasionally in hepatocytes and bile canaliculi. Electron microscopy demonstrated aggregated protoporphyrin crystals at these sites as well as membrane blebs and reduction of microvilli in bile canaliculi. In contrast, experimental mice that were concomitantly fed cholic acid and griseofulvin developed no detectable pigment on light microscopy, only rare protoporphyrin crystals on electron microscopy and minimal bile canalicular abnormalities. This study suggests that protoporphyrin transport into bile is enhanced by cholic acid treatment and results in a significant reduction in hepatic protoporphyrin deposition and associated abnormalities of liver morphology.