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Cytochrome P450S and Alcoholic Liver Disease

[ Vol. 24 , Issue. 14 ]

Author(s):

Yongke Lu* and Arthur I. Cederbaum   Pages 1502 - 1517 ( 16 )

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.

Affiliation:

Department of Health Sciences, College of Public Health, East Tennessee State University Johanson City, TN37614, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, Newyork



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