Dynamics of cytochrome P4502E1 activity in man:: induction by ethanol and disappearance during withdrawal phase
Dynamics of cytochrome P4502E1 activity in man:: induction by ethanol and disappearance during withdrawal phase
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DOI：
10.1016/s0168-8278(01)00223-9
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发表时间：
2002-01-01
影响因子：
25.7
通讯作者：
Seitz, HK
中科院分区：
文献类型：
--
作者：
Oneta, CM;Lieber, CS;Seitz, HK
背景/目的：慢性乙醇消耗导致人类肝细胞色素P4502E1 （CYP2E1）的诱导，被认为在酒精性肝病的发病机制中起重要作用。然而，与CYP2E1诱导相关的酒精摄入量和持续时间尚不清楚，但关于酒精戒断后CYP2E1消失的信息有限。方法：为了研究这些问题，5名健康男性志愿者在4周内每天服用乙醇（40 g/天）。在开始饮酒前和饮酒后每周采用氯唑唑酮试验监测CYP2E1诱导。此外，还测定了5名酒精戒断后1、3、8和15天的酗酒者和5名非酒精性肝病患者的CYP2E1水平。结果：每天摄入40 g乙醇后1周出现显著的CYP2E1诱导，4周后进一步增强。在酒精戒断后3天，CYP2E1明显消失，并在第8天进一步下降。此后，没有发生显著变化，CYP2E1活性与非酒精性肝病患者相当。结论：这些数据显示CYP2E1活性的显著和快速诱导，已经在适度饮酒，这可能是重要的酒精性肝病的发病机制，乙醇，药物和维生素a的相互作用，并在酒精相关的致癌作用。(C) 2002年欧洲肝脏研究协会。Elsevier Science B.V.版权所有。
Background/Aims: Chronic ethanol consumption results in the induction of hepatic cytochrome P4502E1 (CYP2E1) in man, which is believed to play an important role in the pathogenesis of alcoholic liver disease. However, the amount and duration of alcohol intake associated with CYP2E1 induction is not known but limited information is available on the disappearance of CYP2E1 following alcohol withdrawal.Methods: To study these questions, five healthy male volunteers received ethanol daily (40 g/day) over 4 weeks. CYP2E1 induction was monitored by using the chlorzoxazone test before and every week following the start of alcohol ingestion. In addition, CYP2E1 was also determined in five alcoholics 1, 3, 8 and 15 days following ethanol withdrawal and in five patients with non-alcoholic liver disease.Results: A significant CYP2E1 induction occurred 1 week following the ingestion of 40 g ethanol per day and increased further after 4 weeks. The disappearance of CYP2E1 was found to be significant 3 days following ethanol withdrawal and further decreased up to day 8. Thereafter, no significant change occurred and CYP2E1 activities were comparable with those in patients with non-alcoholic liver disease.Conclusions: These data show a significant and quick induction of CYP2E1 activity, already at moderate alcohol consumption, which may be of importance in the pathogenesis of alcoholic liver disease, of ethanol, drug and vitamin A interactions and in alcohol associated carcinogenesis. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.