Effect of Barakol on Cytochrome P450, UDP-Glucuronyltransferase and Glutathione S-Transferase in Isolated Rat Hepatocytes

Abstract

Effect of barakol at various concentrations (0.025, 0.05, 0.075, 0.10 and 0.15 mM) was studied directly in isolated rat hepatocytes by determining the activities of phase 1 enzyme, aminopyrine N-demethylase (CYP2B, CYP2C),and phase II enzymes including UDPglucuronyltransferase and glutathione S-transferase. The release of cellular transaminase(ALT,AST), the reduced glutathione (GSH) contents and the extent of lipid peroxidation(as indicated by malondialdehyde (MDA) formation) were also measured and regarded as thecytotoxic criteria. Results indicated that barakol at all concentrations studied, increased the activities of aminopyrine N-demethylase and glutathione S-transferase with the reduction in UDP-glucuronyltransferase activity. Increase in the release of ALT, AST and GSH contents were found only with high concentrations of barakol (0.10 and 0.15 mM). There was no change in MDA formation. In conclusion, cytotoxicity induced by high concentrations of barakol may involve the activities of certain phase I and phase II enzymes but not the lipid peroxidation.