ROLE OF ENDOTHELIN IN OBSTRUCTIVE JAUNDICE

Abstract

Mediators responsible for renal changes in obstructive jaundice are not specified. This study is designed to study the role of Endothelin-1 (ET-1) in obstructive jaundice in rats. Animals were randomly placed into five experimental groups. Group 1 (n=3) was the sham operated group. Group 2 (n=8) after common bile duct (CBD) ligation, received Bosentan, which is a non selective endothelin receptor blocker, 50 mgr/kg/day for seven days. Group 3 (n=7) received 1microgr/kg/day Captopril. Group 4 (n=7) were given both drugs orally for seven days. Group 5 (n=6) after CBD ligation, received Arabic Gum as the vehicle. Blood was taken from the infrahepatic vena cava for the determination of ET-1, bilirubin, creatinine, protein oxidation products, hyaluronic acid, and beta p-N-acetyl-hexosaminase (Beta-NAH). Liver tissue samples were obtained to determine glutathione levels. ET-1, protein oxidation products, hyaluronic acid, bilirubin, and creatinine levels increased significantly in the control group when compared with sham. Bosentan effectively prevented ET-1 elevation but could not reverse creatinine or bilirubin elevation. Captopril with or without Bosentan was cytoprotective but did not reverse increased creatinine levels. It is concluded that increased ET-1 in obstructive jaundice may be one of the contributing factors of renal damage.