THROMBOXANE INHIBITORS ATTENUATE PATHOLOGICAL-CHANGES IN ALCOHOLIC LIVER-DISEASE IN THE RAT

Background & Aims: Thromboxane levels correlate with severity of liver injury in rats given alcohol, The aim of this study was to evaluate t he effect of thromboxane inhibitors on pathological changes in experim ental alcoholic liver disease, Methods: Male Wistar rats were given a liquid diet and ethanol intragastrically for 1 month, The thromboxane inhibitors tested were a thromboxane receptor antagonist (TXRA) and a thromboxane synthase inhibitor (TXSI), Pathological changes, liver and plasma thromboxane levels, 6-keto-prostaglandin F-1 alpha levels, lip id peroxidation, and messenger RNA levels for tumor necrosis factor (T NF)-alpha and transforming growth factor (TGF) beta were evaluated, Re sults: Treatment with thromboxane inhibitors prevented necrosis and in flammation, In the TXSI-treated group, fatty liver was also decreased, Ethanol administration led to a 3-4-fold increase in liver thromboxan e levels; a reduction in thromboxane revels and lipid peroxidation was seen in the TXSI group. In all treatment groups, TNF-alpha and TGF-be ta messenger RNA levels were decreased, Conclusions: The prevention of necro-inflammatory changes in thromboxane-treated groups is related t o a decrease in TNF-alpha levels. Inhibition of TGF-beta expression ma y also prevent fibrosis in ethanol-treated rats.