Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model
Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model
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DOI：
10.1016/s0378-8741(98)00210-4
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发表时间：
1999-10-01
影响因子：
5.4
通讯作者：
Li, RC
中科院分区：
文献类型：
--
作者：
Zhu, M;Lin, KF;Li, RC
为了评价北五味子在CCl 4损伤肝脏中恢复肝脏药物代谢的潜在活性，以安替比林为探针，研究了北五味子对大鼠I相氧化代谢的可能影响。雄性Sprague-Dawley大鼠（220-240 g）在CCl 4中毒（4 ml/kg，s.c.）前30 min或6 h经口给予五味子木脂素组分（160 mg/kg）。对肝损伤大鼠单次口服安替比林（80 mg/kg）后，测定全血中安替比林的药代动力学，并测定肝酶（如SGPT、SGOT和细胞色素P-450）的水平。使用非房室分析估计安替比林的药代动力学参数。结果表明，与对照组相比，CCl_4使安替比林的消除半衰期（t（1/2））从2.59 +/- 1.04增加到11.25 +/- 3.91 h（P < 0.001），清除率（CL）从65.94 ml/h降低到10.84 ml/h。在中毒前30分钟或6小时用五味子木脂素级分预处理显著（P < 0.001）改善安替比林消除，其t（1/2）分别降低至3.30 +/- 0.52和3.58 +/- 1.05小时。观察到CL的相应改善，即49.06 +/- 21.75 ml/h（P < 0.01）; 21.10 +/- 10.42 ml/h（P < 0.05），也是显著的。此外，正常化的SGPT，SGOT和P-450水平与两个五味子预处理方案观察。综上所述，五味子木脂素对四氯化碳损伤的肝脏I相氧化代谢具有较强的保护作用。此外，五味子预处理中毒前30分钟表现出更明显的效果比6小时的预处理。目前的药代动力学方法允许五味子对受损肝脏中氧化药物代谢的保护作用进行系统检查，并且肯定有助于评估从天然来源获得的保肝药。(C)1999由Elsevier Science爱尔兰有限公司出版。保留所有权利。
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 P-450 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 a 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 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. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.