Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl 4 intoxication model

Abstract

To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl 4 damaged liver, antipyrine was employed as a probe for the possible effects of the herb on Phase I oxidative metabolism in rats. Schisandra lignan fraction (160 mg/kg) was given orally to male Sprague–Dawley rats (220–240 g) 30 min or 6 h before CCl 4 intoxication (4 ml/kg, s.c.). Following a single oral dose of antipyrine (80 mg/kg) to the rats with damaged liver, the pharmacokinetics of antipyrine in whole blood were determined and levels of liver enzymes, e.g. SGPT, SGOT, and cytochrome P 450 were measured. Pharmacokinetic parameters for antipyrine were estimated using noncompartmental analysis. Results indicated that CCl 4 significantly increased the elimination half-life ( t 1/2) of antipyrine from 2.59±1.04 to 11.25±3.91 h ( P<0.001) and decreased its clearance (CL) from 65.94 to 10.84 ml/h as compared to control. Pretreatment with the Schisandra lignan fraction 30 min or 6 h before intoxication significantly ( P<0.001) improved antipyrine elimination by reducing its t 1/2 to 3.30±0.52 and 3.58±1.05 h, respectively. The corresponding improvements observed for CL, i.e. 49.06±21.75 ml/h ( P<0.01); 21.10±10.42 ml/h ( P<0.05), were also substantial. Moreover, normalization of SGPT, SGOT and P 450 levels was observed with the two Schisandra pretreatment schedules. In conclusion, Schisandra lignans exhibited strong protective effect on Phase I oxidative metabolism in the liver damaged by CCl 4. Furthermore, pretreatment of Schisandra 30 min before intoxication showed a more pronounced effect than that of the 6 h pretreatment. The current pharmacokinetic approach allowed the protective effects of Schisandra on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the evaluation of hepato-protectants obtained from natural sources.