PGE 2 alleviates kidney and liver damage, decreases plasma renin activity and acute phase response in cirrhotic rats with acute liver damage

Abstract

In this study, we evaluated the effect of prostaglandin E 2 (PGE 2) on renal and hepatic function using an experimental cirrhosis model plus acute liver damage (ALD). Male Wistar rats treated with carbon tetrachloride (CCl 4) for 8 weeks were used for the cirrhosis model. Cirrhotic rats were further exposed to an additional acute dose of CCl 4 to induce ALD and then treated with PGE 2 intramuscularly twice a day for 7 days (200 μg/Kg/day). PGE 2 administration started 3 h after the additional dosing of CCl 4 and PGE 2 effect on hepatorenal function was examined on days 1, 2, 3, and 7. PGE 2-treatment ameliorated the decrease in urinary sodium excretion, and normalized serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and plasma renin observed in cirrhotic rats with ALD. In addition, PGE 2-treatment decreased mean arterial pressure, glomerular hypercellularity and thickening of the kidney capillary wall, and liver steatosis and cellular necrosis. Also, PGE 2 increased the number of regenerative nodules. Finally, PGE 2-treatment inhibited the increase in Alpha 1-acid glycoprotein (pAGP), fibrinogen, and Apo A-1 mRNA expression by 83%, 59%, and 77%, respectively. These results suggest that PGE 2 administration may decrease the expression of acute phase proteins. In conclusion, PGE 2-treatment improved hepatic and renal function and may be useful to down-regulate the acute phase response in cirrhotic rats presenting ALD induced by CCl 4.