Abstract
Alcohol consumption causes liver diseases, designated as Alcoholic Liver Disease (ALD). Because alcohol is detoxified by alcohol dehydrogenase (ADH), a major ethanol metabolism system, the development of ALD was initially believed to be due to malnutrition caused by alcohol metabolism in liver. The discovery of the microsomal ethanol oxidizing system (MEOS) changed this dogma. Cytochrome P450 enzymes (CYP) constitute the major components of MEOS. Cytochrome P450 2E1 (CYP2E1) in MEOS is one of the major ROS generators in liver and is considered to be contributive to ALD. Our labs have been studying the relationship between CYP2E1 and ALD for many years. Recently, we found that human CYP2A6 and its mouse analog CYP2A5 are also induced by alcohol. In mice, the alcohol induction of CYP2A5 is CYP2E1-dependent. Unlike CYP2E1, CYP2A5 protects against the development of ALD. The relationship of CYP2E1, CYP2A5, and ALD is a major focus of this review.
Keywords: Alcohol induction, antioxidants, CYP2A5, CYP2A6, CYP2E1, Nrf2, reactive oxygen species, interactions, pyrazole, alcoholic liver disease, liver fibrosis, nicotine, PPARα, FGF21, LPS, TNFα, MAPK, HIF-1α, autophagy, coumarin 7-hydroxylase.
Current Pharmaceutical Design
Title:Cytochrome P450S and Alcoholic Liver Disease
Volume: 24 Issue: 14
Author(s): Yongke Lu*Arthur I. Cederbaum
Affiliation:
- Department of Health Sciences, College of Public Health, East Tennessee State University Johanson City, TN37614,United States
Keywords: Alcohol induction, antioxidants, CYP2A5, CYP2A6, CYP2E1, Nrf2, reactive oxygen species, interactions, pyrazole, alcoholic liver disease, liver fibrosis, nicotine, PPARα, FGF21, LPS, TNFα, MAPK, HIF-1α, autophagy, coumarin 7-hydroxylase.
Abstract: Alcohol consumption causes liver diseases, designated as Alcoholic Liver Disease (ALD). Because alcohol is detoxified by alcohol dehydrogenase (ADH), a major ethanol metabolism system, the development of ALD was initially believed to be due to malnutrition caused by alcohol metabolism in liver. The discovery of the microsomal ethanol oxidizing system (MEOS) changed this dogma. Cytochrome P450 enzymes (CYP) constitute the major components of MEOS. Cytochrome P450 2E1 (CYP2E1) in MEOS is one of the major ROS generators in liver and is considered to be contributive to ALD. Our labs have been studying the relationship between CYP2E1 and ALD for many years. Recently, we found that human CYP2A6 and its mouse analog CYP2A5 are also induced by alcohol. In mice, the alcohol induction of CYP2A5 is CYP2E1-dependent. Unlike CYP2E1, CYP2A5 protects against the development of ALD. The relationship of CYP2E1, CYP2A5, and ALD is a major focus of this review.
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Cite this article as:
Lu Yongke *, Cederbaum I. Arthur , Cytochrome P450S and Alcoholic Liver Disease, Current Pharmaceutical Design 2018; 24 (14) . https://dx.doi.org/10.2174/1381612824666180410091511
DOI https://dx.doi.org/10.2174/1381612824666180410091511 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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