Ethanol enhancement of cocaine-induced hepatotoxicity.
Ethanol enhancement of cocaine-induced hepatotoxicity.
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乙醇增强可卡因引起的肝毒性。
DOI：
10.1016/0006-2952(81)90630-4
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发表时间：
1981
影响因子：
5.8
通讯作者：
Harbison,RD
中科院分区：
文献类型：
--
作者：
Smith,AC;Freeman,RW;Harbison,RD
成年雄性小鼠给予乙醇（在流质饲料中给予4.3%乙醇5天），血液乙醇浓度峰值为180 mg/100 ml，并导致肝脏细胞色素P-450水平显着增加。乙醇治疗显著降低可卡因诱导的急性致死率从67%到23%.However，乙醇治疗导致潜在的（1-7天）可卡因诱导的毒性增强，其特征为肝功能障碍，如血清谷丙转氨酶（SGPT）活性所监测，以及深刻的小叶中心坏死。引起SGPT活性升高的可卡因的最小剂量为20 mg/kg，i. p.;最大升高的SGPT活性产生的剂量为40毫克/公斤，i. p.的SGPT活性的峰值升高出现在24和30小时之间的可卡因给药后。在给予30 mg/kg可卡因后观察到明显的肝坏死。乙醇增强可卡因诱导的肝毒性依赖于肝细胞色素P-450混合功能氧化酶系统的诱导。可卡因引起的肝坏死的小叶内位置也依赖于所使用的诱导剂。乙醇增强可卡因诱导的延迟毒性，可能是通过增强其生物转化为产生肝小叶中心坏死的化学反应性中间代谢产物。
Ethanol administration (4.3% ethanol in a liquid diet for 5 days) to adult male mice produced a peak blood ethanol concentration of 180 mg/100 ml and resulted in a significant increase in hepatic cytochrome P-450 levels. Ethanol treatment significantly reduced cocaine-induced acute lethality from 67 to 23 per cent. However, ethanol treatment resulted in a potentiation of a latent (1–7 day) cocaine-induced toxicity characterized by hepatic dysfunction, as monitored by serum glutamate-pyruvate transaminase (SGPT) activity, and a profound centrilobular necrosis. The minimum dose of cocaine that caused elevations of SGPT activity was 20 mg/kg, i.p.; maximum elevations of SGPT activity were produced by a dose of 40 mg/kg, i.p. The peak elevations of SGPT activity were seen between 24 and 30 hr following adminstration of cocaine. Frank hepatic necrosis was seen following administration of 30 mg/kg of cocaine. Ethanol potentiation of cocaine-induced hepatoxicity was dependent on induction of the hepatic cytochrome P-450 mixed function oxidase enzyme system. The intralobular location of the cocaine-induced hepatic necrosis was also dependent upon the inducing agent used. Ethanol potentiated the cocaine-induced delayed toxicity presumably by enhancing its biotransformation to a chemically reactive intermediate metabolite that produced the hepatic centrilobular necrosis.
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统计推断 I.
DOI：
--
发表时间：
1964
期刊：
影响因子：
--
作者：
B. Harshbarger;C. Jerome
通讯作者：
C. Jerome
影响因子：
6
作者：
O. Iseri;C. Lieber;L. Gottlieb
通讯作者：
L. Gottlieb
酒精引起人类肝脏的早期精细结构变化。
影响因子：
29.4
作者：
E. Rubin;C. Lieber
通讯作者：
C. Lieber
人和大鼠长期服用乙醇后乙醇、甲丙氨酯和戊巴比妥代谢增加。
影响因子：
5.9
作者：
P. Misra;A. Lefèvre;H. Ishii;E. Rubin;C. Lieber
通讯作者：
C. Lieber
高蛋白和低脂肪饮食的男性酒精性脂肪肝。
影响因子：
5.9
作者：
C. Lieber;E. Rubin
通讯作者：
E. Rubin