Biphenyl Dimethyl Dicarboxylate가 간내 Cytochrome P450 1A1과 2B1 및 CCl4 유도 간독성에 미치는 영향 = Effect of Biphenyl Dimethyl Dicarboxylate on Cytochrome P450 1A1 and 2B1 and CCl4-Induced Hepatotoxicity in Rat Liver

다국어 초록 (Multilingual Abstract)

In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome P450 1A1 and 2B1, and the protective mechanism against CCl4-induced hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1-7 days) and with different doses (25, 50, 100 and 200mg/kg), mRNA levels of CYP1A1 and CYP2B1 were measured by polymerase chain reaction (PCR) and assayed the activities of CYP1A1 specific ethoxyresorufin-0-dealkylase (EROD) and CYP2B1 specific benzyloxyresorufin-0-dealkylase (BROD). DDB treatment resulted in increase in CYP2B1 mRNA level and BROD activity, whereas there was no change in CYP1A1 mRNA level and EROD activity. This effect of DDB was time- and dose-dependent and reached maximal level by 3 day and 200mg/kg treatment. In addition, rats were pretreated with DDB at doses of 25, 50 or 100mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, CCl4 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on CCl4-induced hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde (MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50mg/kg appeared the most protective effect against CCl4-induced hepatotoxity. These results indicate that DDB stimulates CYP2B1 mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on CCl4-induced hepatotoxicity may be mediated through free radical scavenging.