PGE2 alleviates kidney and liver damage, decreases plasma renin activity and acute phase response in cirrhotic rats with acute liver damage.
In this study, we evaluated the effect of prostaglandin E2 (PGE2) on renal and hepatic function using an experimental cirrhosis model plus acute liver damage (ALD). Male Wistar rats treated with carbon tetrachloride (CCl4) for 8 weeks were used for the cirrhosis model. Cirrhotic rats were further exposed to an additional acute dose of CCl4 to induce ALD and then treated with PGE2 intramuscularly twice a day for 7 days (200 microg/Kg/day). PGE2 administration started 3 h after the additional dosing of CCl4 and PGE2 effect on hepatorenal function was examined on days 1, 2, 3, and 7. PGE2-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, PGE2-treatment decreased mean arterial pressure, glomerular hypercellularity and thickening of the kidney capillary wall, and liver steatosis and cellular necrosis. Also, PGE2 increased the number of regenerative nodules. Finally, PGE2-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 PGE2 administration may decrease the expression of acute phase proteins. In conclusion, PGE2-treatment improved hepatic and renal function and may be useful to down-regulate the acute phase response in cirrhotic rats presenting ALD induced by CCl4.
Rincón-Sánchez
Ana Rosa
AR
Institute of Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco 44281, México. arrincon@cencar.udg.mx
Covarrubias
Amador
A
Rivas-Estilla
Ana María
AM
Pedraza-Chaverrí
José
J
Cruz
Cristino
C
Islas-Carbajal
María Cristina
MC
Panduro
Arturo
A
Estanes
Alma
A
Armendáriz-Borunda
Juan
J
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000187:drug effects*; D000818:Animals; D015152:Blotting, Northern; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D015232:Dinoprostone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood / Q000187:drug effects*
D000209:Acute-Phase Proteins; D002251:Carbon Tetrachloride; D012083:Renin; D015232:Dinoprostone