Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2005; 11(29): 4530-4535
Published online Aug 7, 2005. doi: 10.3748/wjg.v11.i29.4530
CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes
Lie-Gang Liu, Hong Yan, Ping Yao, Wen Zhang, Li-Jun Zou, Fang-Fang Song, Ke Li, Xiu-Fa Sun
Lie-Gang Liu, Hong Yan, Ping Yao, Wen Zhang, Li-Jun Zou, Fang-Fang Song, Ke Li, Xiu-Fa Sun, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Science Foundation of China, No. 30271130
Correspondence to: Dr. Lie-Gang Liu, Department of Nutrition and Food Hygiene, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. lgliu@mails.tjmu.edu.cn
Telephone: +86-27-83692711 Fax: +86-27-83693307
Received: May 25, 2004
Revised: June 12, 2004
Accepted: June 17, 2004
Published online: August 7, 2005
Abstract

AIM: To observe the relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and cytochrome P450 2E1 (CYP2E1) activity, in order to address if inhibition of CYP2E1 could attenuate ethanol-induced cellular damage.

METHODS: The dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) exposures of primary human cultured hepatocytes to ethanol were carried out. CYP2E1 activity and protein expression were detected by spectrophotometer and Western blot analysis respectively. Hepatotoxicity was investigated by determination of lactate dehydrogenase (LDH) and aspartate transaminase (AST) level in hepatocyte culture supernatants, as well as the intracellular formation of malondialdehyde (MDA).

RESULTS: A dose-and time-dependent response between ethanol exposure and CYP2E1 activity in human hepatocytes was demonstrated. Moreover, there was a time-dependent increase of CYP2E1 protein after 100 mmol/L ethanol exposure. Meanwhile, ethanol exposure of hepatocytes caused a time-dependent increase of cellular MDA level, LDH, and AST activities in supernatants. Furthermore, the inhibitor of CYP2E1, diallyl sulfide (DAS) could partly attenuate the increases of MDA, LDH, and AST in human hepatocytes.

CONCLUSION: A positive relationship between ethanol-induced oxidative damage in human primary cultured hepatocytes and CYP2E1 activity was exhibited, and the inhibition of CYP2E1 could partly attenuate ethanol-induced oxidative damage.

Keywords: Ethanol; CYP2E1; Oxidative damage; Human primary hepatocytes