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Long‐Term Binge and Escalating Ethanol Exposure Causes Necroinflammation and Fibrosis in Rat Liver
Author(s) -
Zhou JunYing,
Jiang ZhiAn,
Zhao CaiYan,
Zhen Zhen,
Wang Wei,
Nanji Amin A.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01936.x
Subject(s) - proinflammatory cytokine , oxidative stress , steatosis , endocrinology , medicine , tumor necrosis factor alpha , fibrosis , alcoholic liver disease , inflammation , pathogenesis , cyclooxygenase , chemistry , cirrhosis , biochemistry , enzyme
Background To investigate whether “binge” and escalating alcohol exposure in the rat influences the development of pathological liver injury. Methods Time courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative stress and nitrosative stress production, expression of hypoxia‐inducible factor 1 (HIF‐1), cytokines, hepatic tissue necroinflammation, and fibrosis were assessed in rats during 16 weeks of daily alcohol gavage. Results In this model of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and inflammation as well as fibrosis were increased over the 16‐week period. The levels of COX‐2, oxidative stress, nitrosative stress, HIF‐1, proinflammatory mediators ( tumor necrosis factor ‐α, interleukin 1 β [IL‐1 β ], IL‐6), and procollagen‐I were increased over the 16‐week period. The content of IL‐10 in rat serum increased at the end of 4 and 8 weeks but decreased thereafter and was significantly decreased at 12 and 16 weeks. Conclusions A rat model of alcoholic liver disease (ALD) with long‐term binge and escalating ethanol exposure was developed. Our data support the hypothesis that enhanced eicosanoid production by COX, oxidative stress and nitrosative stress, HIF‐1, and the imbalance between pro‐ and anti‐inflammatory cytokines plays an important role in the pathogenesis of ALD.