Comparison of the effects of griseofulvin and dihydropyridines on ferrochelatase activity and porphyrin accumulation in primary cultures of mouse and rat hepatocytes

摘要: The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethyl pyridine (EDDC) and griseofulvin to induce porphyria in primary cultures mouse rat hepatocytes was determined. Exposure DDC, EDDC or (5-100 mum) for 4 days resulted a marked inhibition ferrochelatase activity (up 95%). However, whereas exposure DDC also 96%), had no effect. induced porphyrin accumulation both hepatocyte cultures. In exposed each xenobiotic the that accumulated predominantly protoporphyrin. protoporphyrin, following it coproporphyrin. Time course studies confirmed (25 100 over 4-day period, not inhibited coproporphyrin always predominant accumulating (45-72% total). Addition 5-aminolaevulinic acid (10-1000 but uroporphyrin cultures, These demonstrated hepatic porphyrias produced by dihydropyridines can be modelled vitro hepatocytes. Furthermore, species differences sensitivity mirrors, therefore probably explains, observed vivo.