Background: Cholestasis caused by reduced flow of bile, which leads to accumulation of bile acids and other chemicals in liver and blood. It is one of the most common and devastating manifestations among hereditary and acquired liver diseases, and it ultimately leads to liver damage, fibrosis, cirrhosis and death. Hydrophobic bile acids may cause hepatocellular necrosis and apoptosis during cholestatic liver diseases. The mechanism for this injury involve mitochondrial dysfunction and oxidative stress. Mitochondria are extremely dynamic organelles which in healthy cells are constantly dividing and re-combined to form an dynamic interconnected network. This processes called mitochondrial fission and fusion. Drp1 is one of the gene involved in mitochondrial fission and plays a role in apoptosis. Drp1 gene expression in the liver of cholestatic rats were examined in this study. Materials and Methods: The Male Wistar rats (280-340g) were used into three groups of control (non-operated), sham (operated without common bile duct ligation) and BDL (operated with common bile duct ligation). On day 24 of BDL, rats were weighed and sacrificed. Biochemical assays and dissection of liver tissue for histopathological analysis and Drp1 gene expression evaluation by semi-quantitative RT-PCR technique were performed. Results: The results revealed that serum levels of total Bilirubin and liver enzymes (ALT, AST ,ALK) were significantly increased in BDL group as compared with the control and sham operation groups (P<0.01).Concerning histology, the appearance of biliary ductular hyperplasia, periductular inflammation and focal hepatocyte necrosis were noted with BDL group. The result also showed that the Drp1 gene expression in liver of BDL rats was significantly increased as compared with other groups (P<0.001).Conclusion: This study shows that an increase in gene expression level of Drp1 can result from to mitochondrially-mediated apoptotic effect of high concentration of toxic bile
