ABSTRACT
Background and Aim: Cholestasis is characterized by impaired bile flow, which can cause accumulation of bile acids in the liver and development of metabolic disorders, resulting in hepatocellular necrosis and apoptosis. Mitochondria are a critical cellular organelle that produces most of the cellular energy. Mitochondrial morphology varies from an interconnected filamentous network to isolated dots. This processes are called mitochondrial fission and fusion. Disrupted mitochondrial morphology has been observed in cholestatic liver disease. Dynamin related protein 1 is one of the genes involved in mitochondrial fission and plays a role in apoptosis. In this study we investigated Drpl gene expression in the liver of cholestatic rats
Materials and Methods: In this experimental study, male Wistar rats [290+/-25g] were divided into three groups of control [non-operated], sham [operated without common bile duct ligation] and BDL [operated with common bile duct ligation]. On the 28[th] day of BDL, rats were weighed and sacrificed. Biochemical assays for measurement of bilirubin level and liver enzymes, and also dissection of liver tissue for histopathological analysis were performed. Drpl gene expression was evaluated by semi-quantitative RT-PCR technique
Results: The results showed that serum levels of total bilirubin and liver enzymes [ALT, AST, ALK] were significantly increased in BDL group compared to those in the control and sham operation groups [P<0.0001 and P<0.001]. Histological examination revealed bile ductular hyperplasia, focal liver necrosis and fibrous tissue expansion in BDL group. The result of RT-PCR indicated significant increase of Drpl gene expression in the liver of the rats in BDL group compared to that in the other groups [P<0.001
Conclusion: In this study we found that liver cholestasis increased expression of Drpl gene which led to increased mitochondrial-mediated apoptotic effect with resultant liver cell death