Role of eicosanoids in experimental alcoholic liver disease

Based on our previous observations that linoleic acid is an important dietary requirement for the development of liver injury in the intragastric feeding rat model for alcoholic liver disease, we postulated that the conversion of linoleic acid to arachidonic acid and various eicosanoids could be important in the pathogenesis of liver injury. We showed that liver nonparenchymal cell production of thromboxane B₂ and leukotriene B₄ was higher in rats fed corn oil and ethanol (liver injury model) than in animals fed saturated fat and ethanol (no liver injury). In contrast, prostaglandin E₂ levels were lower in the former group. The best correlate of pathologic changes was the plasma level of thromboxane B₂. The importance of thromboxanes in alcoholic liver injury is further suggested by the fact that inhibition of thromboxane production is accompanied by amelioration of liver injury.