Selective protection of curcumin against carbon tetrachloride-induced inactivation of hepatic cytochrome P450 isozymes in rats

We investigated the effects of curcumin, a major antioxidant constituent of turmeric, on hepatic cytochrome P450 (CYP) activity in rats. Wistar rats received curcumin-containing diets (0.05, 0.5 and 5 g/kg diet) with or without injection of carbon tetrachloride (CCl4). The hepatic CYP content and activities of six CYP isozymes remained unchanged by curcumin treatment, except for the group treated with the extremely high dose (5 g/kg). This suggested that daily dose of curcumin does not cause CYP-mediated interaction with co-administered drugs. Chronic CCl4 injection drastically decreased CYP activity, especially CYP2E1 activity, which is involved in the bioactivation of CCl4, thereby producing reactive free radicals. Treatment with curcumin at 0.5 g/kg alleviated the CCl4-induced inactivation of CYPs 1A, 2B, 2C and 3A isozymes, except for CYP2E1. The lack of effect of curcumin on CYP2E1 damage might be related to suicidal radical production by CYP2E1 on the same enzyme. It is speculated that curcumin inhibited CCl4-induced secondary hepatic CYPs damage through its antioxidant properties. Our results demonstrated that CYP isozyme inactivation in rat liver caused by CCl4 was inhibited by curcumin. Dietary intake of curcumin may protect against CCl4-induced hepatic CYP inactivation via its antioxidant properties, without inducing hepatic CYPs.