TY - JOUR T1 - Alterations in Thromboxane Synthase and Thromboxane A<sub>2</sub> Receptors in Experimental Alcoholic Liver Disease JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1037 LP - 1043 VL - 282 IS - 2 AU - Amin A. Nanji AU - Amir Rahemtulla AU - Lili Maio AU - Shamsuddin Khwaja AU - Shuping Zhao AU - Steven R. Tahan AU - Peter Thomas Y1 - 1997/08/01 UR - http://jpet.aspetjournals.org/content/282/2/1037.abstract N2 - We have previously shown that hepatic thromboxane production is increased in experimental alcoholic liver disease. The present study was designed to investigate the cell type in liver responsible for increased thromboxane synthesis and the role of the thromboxane receptor system in the pathogenesis of liver injury. Male Wistar rats were divided into four groups and fed a liquid diet with dextrose or ethanol for 2, 4 and 8 weeks. Medium chain triglycerides or corn oil provided the dietary fatty acids. Kupffer cells, endothelial cells and hepatocytes were isolated from rats fed the different diets for 4 weeks. Liver histopathology, thromboxane synthase mRNA and protein, thromboxane levels and thromboxane receptor mRNA were evaluated in each group. In rats fed corn oil and ethanol, an increase in thromboxane synthase and liver levels of thromboxane metabolites were significantly higher than in the corn oil-dextrose-fed group and were correlated with the presence of pathological changes in the liver. Kupffer cells showed increased expression of thromboxane synthase. In rats fed medium chain triglycerides and ethanol, the levels of thromboxane synthase mRNA and protein were significantly lower than in the corn oil-ethanol-fed groups (P &lt; .01) and liver injury was absent. However, the levels of thromboxane synthase mRNA, protein and thromboxane were significantly higher in the medium chain triglyceride-ethanol-fed rats than in the respective dextrose-fed controls. Among the different cell types, thromboxane A2-receptor mRNA levels were highest in the Kupffer cells in corn oil-ethanol-fed rats. The increase in thromboxane synthase in Kupffer cells together with an increase in thromboxane receptor levels suggests than thromboxanes may contribute to liver injury in ethanol-fed rats. The American Society for Pharmacology and Experimental Therapeutics ER -