Effect of Alpha-Lipoic acid on Pancreatic Optic Atrophy 1 (OPA1) Gene Expression in Male Rat Model of Obstructive Cholestasis and Cirrhosis

Cholestasis is characterized by blockade of bile flow from the liver to the intestine, which leads to accumulation of bile acids within liver and plasma; it is associated with metabolic disorders and cause hepatocellular necrosis and apoptosis during cholestatic liver diseases. Mitochondria are critical cellular organelles that produce most of the cellular energy. Mitochondrial morphology varies from an interconnected filamentous network to isolated dots. These processes are called mitochondrial fission and fusion. Disrupted mitochondrial morphology has been observed in cholestatic liver disease. Optic Atrophy 1 (OPA1) is one of the proteins involved in mitochondrial fusion and plays an anti-apoptotic role. The aim of this study was to evaluate the effect of α-lipoic acid (LA) on OPA1 gene expression in pancreas of rat after bile duct ligation (BDL).

Thirty-six male Wistar rats were randomly divided into six groups each containing six rats including: control, sham-operated, cholestatic, cholestatic+LA, cirrhotic, and cirrhotic+LA. After 14 days in cholestasis groups and six weeks in cirrhosis groups, serum samples and liver and pancreas tissue samples prepared for total bilirubin assays, histopathological analysis and pancreatic OPA1 gene expression evaluation by Real-time PCR technique. Total bilirubin data and gene expression data were analyzed by one-way ANOVA and Kruskal-Wallis statistical tests. 

The results revealed that serum levels of total Bilirubin were significantly increased in BDL groups as compared with the control and sham operation groups (P<0.0001). Concerning histology, the inflammation Symptoms and tissue necrosis were noted with BDL group. These symptoms were reduced by lipoic acid treatment in the cholestatic group. The result of pancreatic OPA1 gene expression showed the significant increase in cholestatic rats and significant decrease in cirrhotic groups as compared with other groups (P<0.05). In cholestatic group, restoring the expression of OPA1 gene was shown in the presence of lipoic acid.

Changing OPA1 gene expression in obstructive rat suggest the causal role of mitochondrial dynamics in pathogenesis of cholestatic disease. In this study, the effect of lipoic acid in OPA1 mRNA level reflects implications of oxidative stress in signaling pathway of cholestasis.