期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 46, 期 7, 页码 928-938出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2009.01.003
关键词
Liver; Alcohol; Steatosis; Mitochondria; Cigarette smoke; Hypercholesterolemia; Oxidative stress; Hypoxia; Cytochrome c oxidase; Blue native gel electrophoresis; Free radicals
资金
- NIH [AA15172, HL77419, ES11172]
Although epidemiologic Studies indicate that combined exposure to cigarette smoke and alcohol increase the risk and severity of liver diseases, the molecular mechanisms responsible for hepatotoxicity are unknown. Similarly, emerging evidence indicates a linkage among hepatic steatosis and cardiovascular disease. Herein, we hypothesize that combined exposure to alcohol and environmental tobacco smoke (ETS) on a hypercholesterolemic background increases liver injury through oxidative/nitrative stress, hypoxia, and mitochondrial damage. To test this, male apoE(-/-) mice were exposed to an ethanol-containing diet, ETS alone, ora combination of the two, and histology and functional endpoints were compared to filtered-air-exposed, ethanol-naive controls. Whereas ethanol consumption induced a mild steatosis, combined exposure to ethanol + ETS resulted in increased hepatic steatosis, inflammation, alpha-smooth muscle actin, and collagen. Exposure to ethanol + ETS induced the largest increase in CYP2E1 and iNOS protein, as well as increased 3-nitrotyrosine, mtDNA damage, and decreased cytochrome c oxidase protein, compared to all other groups. Similarly, the largest increase in HIF1 alpha expression was observed in the ethanol + ETS group. indicating enhanced hypoxia. These studies demonstrate that ETS increases alcohol-dependent steatosis and hypoxic stress. Therefore, ETS may be a key environmental hit that accelerates and exacerbates alcoholic liver disease in hypercholesterolemic apoE(-/-) mice. (C) 2009 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据