Chronic effects of celecoxib, a cyclooxygenase-2 inhibitor, cause enhanced alcohol-induced liver steatosis in rats

Abstract.

Background: The pathogenetic role of prostaglandins in steatosis, the first stage of alcoholic liver injury, is not well understood, especially that involving the inflammatory reactions controlled by prostaglandins and pro-inflammatory cytokines in the liver. We, therefore, studied the chronic effects of the COX-2 inhibitor, celecoxib, given to ethanol-treated rats. Methods: Rats were fed ethanol and a low dose of celecoxib (~20 mg/kg daily) in a high-fat/low-carbohydrate liquid diet for six weeks. Results: Ethanol treatment caused liver steatosis, moderate cellular infiltration and enhanced levels of plasma alanine transaminase (ALT) and tumour necrosis factor-α (TNF-α). Co-administration of celecoxib further increased the steatosis, relative liver weights and increased plasma ALT and TNF-α levels above those in ethanol-treated rats. Also, celecoxib counteracted the ethanol-induced increase in hepatic prostaglandin E₂ receptor EP4 mRNA expression. In contrast, celecoxib alone increased plasma ALT and TNF-α levels. Conclusions: These results suggest that prolonged low-dose celecoxib treatment with ethanol enhances alcohol-induced steatosis and liver inflammatory reactions above that from ethanol or celecoxib alone. It is suggested that reduction in PGE₂ by treatment with celecoxib removes the endogenous protective effect of this prostaglandin.