The first two authors contributed equally to this work.
Thromboxane Inhibitors Attenuate Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administrations
Article first published online: 7 JUN 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 1, pages 31–39, January 2013
How to Cite
Nanji, A. A., Liong, E. C., Xiao, J. and Tipoe, G. L. (2013), Thromboxane Inhibitors Attenuate Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administrations. Alcoholism: Clinical and Experimental Research, 37: 31–39. doi: 10.1111/j.1530-0277.2012.01838.x
- Issue published online: 4 JAN 2013
- Article first published online: 7 JUN 2012
- Manuscript Accepted: 20 MAR 2012
- Manuscript Received: 28 NOV 2011
- National Institutes of Health. Grant Number: AA 12893
- The University of Hong Kong
- Research Grants Council of the Hong Kong SAR. Grant Number: HKU 7340/00 MM
- Thromboxane Inhibitor;
- Alcoholic Liver Disease;
Thromboxane levels are increased in rats fed ethanol (EtOH), whereas thromboxane inhibitors reduce alcoholic liver injury. The aim of this study is to determine whether thromboxane inhibitors could attenuate the already established alcoholic liver injury.
Rats were fed EtOH and liquid diet for 6 weeks by intragastric infusion to induce liver injury after which EtOH was continued for 2 more weeks, and the rats were treated with either a thromboxane synthase inhibitor (TXSI) or a thromboxane receptor antagonist (TXRA). Liver pathology, lipid peroxidation, nuclear factor-kappa-B (NF-κB) activity, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and transforming growth factor-beta1 (TGF-β1) were evaluated.
Administration of fish oil and EtOH caused fatty liver, necrosis, inflammation and fibrosis accompanied by increased in lipid peroxidation, NF-κB activity, and expression of TNF-α, COX-2, and TGF-β1. Treatment with the thromboxane inhibitors ameliorated a certain level of the pathological and biochemical abnormalities. In particular, TXSI in addition to reducing necrosis, inflammation and fibrosis also decrease the severity of fatty liver.
Thromboxane inhibitors attenuated the alcoholic liver injury, inflammation and fibrotic changes despite continued EtOH administration. Inhibition of the production of thromboxane by thromboxane inhibitor and receptor antagonists may be a useful treatment strategy in clinical alcoholic liver disease.