Long-Term Binge and Escalating Ethanol Exposure Causes Necroinflammation and Fibrosis in Rat Liver
Article first published online: 25 SEP 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 2, pages 213–222, February 2013
How to Cite
Zhou, J.-Y., Jiang, Z.-A., Zhao, C.-Y., Zhen, Z., Wang, W. and Nanji, A. A. (2013), Long-Term Binge and Escalating Ethanol Exposure Causes Necroinflammation and Fibrosis in Rat Liver. Alcoholism: Clinical and Experimental Research, 37: 213–222. doi: 10.1111/j.1530-0277.2012.01936.x
- Issue published online: 1 FEB 2013
- Article first published online: 25 SEP 2012
- Manuscript Accepted: 10 JUN 2012
- Manuscript Received: 3 JUL 2011
- Alcoholic Liver Disease;
- Oxidative Stress;
- Nitrosative Stress;
- Hypoxia-Inducible Factor 1
To investigate whether “binge” and escalating alcohol exposure in the rat influences the development of pathological liver injury.
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.
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 1β [IL-1β], 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.
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.