期刊
ALCOHOL AND ALCOHOLISM
卷 50, 期 2, 页码 118-131出版社
OXFORD UNIV PRESS
DOI: 10.1093/alcalc/agu083
关键词
-
资金
- National Institute of Alcohol Abuse and Alcoholism [AA-11431, AA-12908]
- NIDDK [T32 DK-60415]
- National Cancer Institute [CA-81301]
Aims: Alcoholic liver disease (ALD) is linked to binge drinking and cigarette smoking. Heavy chronic +/- binge alcohol, or low-level exposures to dietary nitrosamines cause steatohepatitis with insulin resistance and oxidative stress in animal models. This study examines hepatotoxic effects of sub-mutagenic exposures to tobacco-specific nitrosamine (NNK) in relation to ALD. Methods: Long Evans rats were fed liquid diets containing 0 or 26% (caloric) ethanol (EtOH) for 8 weeks. In Weeks 3 through 8, rats were treated with NNK (2 mg/kg) or saline by i.p. injection, 3x/week, and in Weeks 7 and 8, EtOH-fed rats were binge-administered 2 g/kg EtOH 3x/week; controls were given saline. Results: EtOH +/- NNK caused steatohepatitis with necrosis, disruption of the hepatic cord architecture, ballooning degeneration, early fibrosis, mitochondrial cytopathy and ER disruption. Severity of lesions was highest in the EtOH+NNK group. EtOH and NNK inhibited insulin/IGF signaling through Akt and activated pro-inflammatory cytokines, while EtOH promoted lipid peroxidation, and NNK increased apoptosis. O-6-methyl-Guanine adducts were only detected in NNK-exposed livers. Conclusion: Both alcohol and NNK exposures contribute to ALD pathogenesis, including insulin/IGF resistance and inflammation. The differential effects of EtOH and NNK on adduct formation are critical to ALD progression among alcoholics who smoke.
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