Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat

Background and Aims: Thromboxane levels correlate with severity of liver injury in rats given alcohol. The aim of this study was to evaluate the effect of thromboxane inhibitors on pathological changes in experimental 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-ketoprostaglandin F(1α) levels, lipid peroxidation, and messenger RNA levels for tumor necrosis factor (TNF)-α and transforming growth factor (TGF) β were evaluated. Results: Treatment with thromboxane inhibitors prevented necrosis and inflammation. In the TXSI-treated group, fatty liver was also decreased. Ethanol administration led to a 3-4-fold increase in liver thromboxane levels; a reduction in thromboxane levels and lipid peroxidation was seen in the TXSI group. In all treatment groups, TNF-α and TGF-β messenger RNA levels were decreased. Conclusions: The prevention of necroinflammatory changes in thromboxane-treated groups is related to a decrease in TNF-α levels. Inhibition of TGF-β expression may also prevent fibrosis in ethanol-treated rats.