مجله علمی دانشگاه علوم پزشکی کردستان (Dec 2019)
Effect of Alpha-Lipoic acidon Pancreatic Optic Atrophy1 (OPA1) Gene Expression in Male Rat Model of Obstructive Cholestasis and Cirrhosis
Abstract
Backgroundand Aim: Cholestasis is characterized by blockade ofbile flowfrom the liver to the intestine, which leads to accumulation of bile acids within liver and plasma; it is associated withmetabolic disordersandcause 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.Theseprocesses are called mitochondrial fission and fusion. Disrupted mitochondrial morphology has been observed in cholestatic liver disease. Optic Atrophy 1 (OPA1) is one of the proteinsinvolved in mitochondrial fusionand plays ananti-apoptotic role. The aim of this study was to evaluate the effect of α-lipoic acid (LA) on OPA1gene expression inpancreasof rat after bile duct ligation(BDL). Materials and Methods:Thirty-six male Wistar rats were randomly divided into sixgroups each containing six rats including: control, sham-operated, cholestatic, cholestatic+LA, cirrhotic, and cirrhotic+LA. After 14 days in cholestasis groups and six weeksin cirrhosis groups, serum samples and liver and pancreastissue samples prepared for total bilirubinassays,histopathological analysis andpancreaticOPA1 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.Results: The results revealed that serum levels of total Bilirubin were significantly increased in BDL groupsas compared with the control and sham operation groups (P<0.0001). Concerning histology, the inflammation Symptoms and tissue necrosiswere noted with BDL group. These symptoms were reduced by lipoic acid treatment in the cholestatic group. The result of pancreatic OPA1 gene expressionshowed the significantincreasein cholestatic rats and significant decrease in cirrhotic groups as compared with other groups (P<0.05).In cholestatic group, restoring the expression of OPA1gene was shown in the presence of lipoic acid.Conclusion:Changing OPA1gene expression in obstructive ratsuggest the causal role of mitochondrial dynamics in pathogenesis of cholestatic disease. In this study, the effectof lipoic acid in OPA1 mRNA levelreflects implications ofoxidative stressin signaling pathway ofcholestasis.
