Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model.
To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl4 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 CCl4 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 P450 were measured. Pharmacokinetic parameters for antipyrine were estimated using noncompartmental analysis. Results indicated that CCl4 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 P450 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 CCl4. 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.
Zhu
M
M
Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Lin
K F
KF
Yeung
R Y
RY
Li
R C
RC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D034242:Cyclooctanes; D005638:Fruit / Q000737:chemistry; D006723:Hong Kong; D017705:Lignans / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional; D015335:Molecular Probes / Q000097:blood; D010084:Oxidation-Reduction / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D034242:Cyclooctanes; D017705:Lignans; D015335:Molecular Probes; D010936:Plant Extracts; D011083:Polycyclic Compounds; D002251:Carbon Tetrachloride; C011105:schizandrin; D000983:Antipyrine