Tıkanma sarılığı modelinde endotelinin rolü

Abstract

SUMMARY Obstructive jaundice is often complicated with renal impairment and complications associated with septic complications due to impaired immune system. The pathophysiology and the mediators taking role in this phenomenon is poorly defined. In this study, the role of endothelins (ET) in obstructive jaundice was investigated in rats. Distal common bile duct was ligated in five groups for seven days. While the control group (n=6) received no medication. Group 1 (n=8) received Bosentan (non selective ETa and ETb receptor antagonist, 50 mg/kg po), Group 2 (n=7) received Kaptopril ( ACE inhibitor, luAg po), Group 3 (n=7) received both agents simultaneously during the course of the study. Sham group (n=3) considered as the last group. On the seventh day serum endothelin-1 levels were measured in inferior vena cava in addition to serum bilirubin, creatinine, GGT, SGOT and protein oxidation levels. Hyaluronic acid (HA) and B-N-acetyl hexosaminidase (B-NAH) were also measured in this sample in order to detect the Kuppfer and sinosoidal cell damage. Glutathione levels were measured in the liver tissue in order to detect the oxidative tissue damage. Results indicate that ET levels increased significantly in the control group when compared with sham group (50.5 vs. 13.8 pg/ml) and Bosentan prevented the increase of ET in the cholestatic rats (28.7 pg/ml). Captopril did not have this effect. Serum protein oxidation, liver function tests and scrum creatinine were all increased in the cholestasis groups indicating the liver and renal fuction failure. As a conclusion, ET appears to be an important mediator in obstructive jaundice which may be responsible for the renal and immune system impairment in obstructive jaiundice. This may partially be prevented by the Bosentan. 39