Effect of ethanol on activity of cytochrome P450 2E1 in Carassius auratus
2007
Chen Dajian | Yang Haifeng | Qin Shaohua
chinois. 为了研究乙醇对鲫鱼细胞色素P450 2E1（CYP2E1）活性的影响，用药动学方法，以氯唑沙宗为底物探针，将130尾鲫鱼随机分为试验组和对照组2组，试验组鲫鱼每日经口灌服乙醇1 g/kg，对照组灌服相同剂量的生理盐水，连续5 d 后，第6天2组鲫鱼同时一次性腹腔注射氯唑沙宗10 mg/kg，于注射后不同时间采血，用高效液相色谱法测定氯唑沙宗在鲫鱼体内不同时间点的血药浓度，并计算药动学参数。结果表明，氯唑沙宗在两组鲫鱼体内的药时数据均符合二室模型；与对照组相比，乙醇处理组氯唑沙宗的半衰期增加了0.9倍（P0.01），药时曲线下面积增加了0.8倍（P0.01），总清除率减少了51.2%（P0.01）。提示乙醇对鲫鱼CYP2E1的活性具有显著的抑制作用。
Afficher plus [+] Moins [-]anglais. The effect of ethanol (EtOH) on the activity of cytochrome P450 2E1 in Carassius auratus was investigated by pharmacokinetics with chlorzoxazone (CZX) as a specific substrate. 130 fish were equally divided into two groups: EtOH-treated group and the control group.EtOH was administered orally to fish at the dose of 1 g/（kg•d） for 5 consecutive days. Fish in control group received an equal volume of normal saline only. On the 6th day, two groups of fish were given an intraperitoneal injection with 10 mg/kg CZX. The plasma concentrations of CZX were determined by HPLC, and the pharmacokinetic parameters were calculated. The results showed that the concentration-time data of CZX in two groups both fitted two compartment models. Compared with the saline-treated control group, elimination half life was increased by 0.9 fold (P0.01), area under the curve was increased by 0.8 fold (P0.01), and total clearance was shortened by 51.2% (P0.01) in the EtOH-treated group. The results indicated that the activity of CYP2E1 could be obviously inhibited by EtOH._
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