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Thromboxane Inhibitors Attenuate Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administrations
Author(s) -
Nanji Amin A.,
Liong Emily C.,
Xiao Jia,
Tipoe George L.
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.1530-0277.2012.01838.x
Subject(s) - thromboxane , liver injury , thromboxane a synthase , thromboxane b2 , medicine , endocrinology , fibrosis , fatty liver , thromboxane a2 , cyclooxygenase , alcoholic liver disease , lipid peroxidation , thromboxane receptor , inflammation , pharmacology , chemistry , receptor , cirrhosis , oxidative stress , biochemistry , platelet , enzyme , disease
Background Thromboxane levels are increased in rats fed ethanol ( E t OH ), 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. Methods Rats were fed E t OH 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 ‐κ B ) activity, tumor necrosis factor‐α ( TNF ‐α), cyclooxygenase‐2 ( COX ‐2), and transforming growth factor‐beta1 ( TGF ‐β 1 ) were evaluated. Results Administration of fish oil and E t OH caused fatty liver, necrosis, inflammation and fibrosis accompanied by increased in lipid peroxidation, NF ‐κ B activity, and expression of TNF ‐α, COX ‐2, and TGF ‐β 1 . 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. Conclusions Thromboxane inhibitors attenuated the alcoholic liver injury, inflammation and fibrotic changes despite continued E t OH administration. Inhibition of the production of thromboxane by thromboxane inhibitor and receptor antagonists may be a useful treatment strategy in clinical alcoholic liver disease.