I L Bykov1, M Palmen, K D Rainsford, K O Lindros. 1. Department of Mental Health and Alcohol Research, Alcohol Research Center, National Public Health Institute, POB 33, 00251 Helsinki, Finland.
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 (approximately 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-alpha (TNF-alpha). Co-administration of celecoxib further increased the steatosis, relative liver weights and increased plasma ALT and TNF-alpha levels above those in ethanol-treated rats. Also, celecoxib counteracted the ethanol-induced increase in hepatic prostaglandin E(2) receptor EP4 mRNA expression. In contrast, celecoxib alone increased plasma ALT and TNF-alpha 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 PGE(2) by treatment with celecoxib removes the endogenous protective effect of this prostaglandin.
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 (approximately 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-alpha (TNF-alpha). Co-administration of celecoxib further increased the steatosis, relative liver weights and increased plasma ALT and TNF-alpha levels above those in ethanol-treated rats. Also, celecoxib counteracted the ethanol-induced increase in hepatic prostaglandin E(2) receptor EP4 mRNA expression. In contrast, celecoxib alone increased plasma ALT and TNF-alpha 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 PGE(2) by treatment with celecoxib removes the endogenous protective effect of this prostaglandin.