THE EFFECTS OF KUPFFER CELL INACTIVATION IN EXPERIMENTAL BILE DUCT OBSTRUCTION

Abstract

Bile duct obstruction is the major cause of chronic cholestasis leading to biliary cirrhosis in childhood. The etiology and treatment of this condition are controversial. The reticuloendothelial system (RES) plays an important role in the biologic defense system. Kupffer cells are the main constituents of the RES in liver. Kupffer inactivation with different agents may decrease the severity of hepatocellular damage in ischemia-reperfusion injury and alcoholic liver diseases. Several reports demonstrated that activated Kupffer cells may cause hepatocellular damage and fibrosis in bile duct obstruction. In this study, Kupffer cells were inactivated by GdCl3 administration to prevent parenchymal damage in experimental model of bile duct obstruction in rats. Thirty-three Male Wistar Rats were divided into three groups, rats in Group1 (n=12) received GdCl3 (7mg/kg, iv.) which is a selective Kupffer cell toxicant, for three weeks following bile duct ligation. Group2 (n=12) received no treatment following bile duct ligation and Group3 (n=9) were sham operated. At the end of the three weeks, weight differences, serum ALT, GGT, ALP, TB, DB, total protein and albumin levels and hydroxy proline levels in liver tissue samples were determined, in addition to histopathological evaluations. In the GdCl3 administrated group, serum ALT, GGT, TB, DB levels were significantly lower in comparison to Group 2. On the other hand, liver tissue hydroxy proline levels and histopathological score of Group1 was significantly lower than Group2. Inflammation, necrosis and fibrosis were reduced dramatically following GdCl3 treatment. We concluded that in experimental model of cholestasis, Kupffer cell inactivation by GdCl3 administration improved the severity of inflammation and fibrosis.