Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins ۲ and ۳

Objective(s): This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP۲ and UCP۳ in cardiac damage induced by cirrhosis. Materials and Methods: Twenty-two male Wistar rats (۲۰۰–۲۵۰ g) were randomly divided into ۳ experimental groups, including a control group (n=۶), a sham-operated group (n=۸), and a bile duct ligated (BDL) group (n=۸). Four weeks after surgical intervention, biochemical assessment (AST, ALT, GGT, LDH, and ALP), histological observation, and molecular evaluation (FXR, UCP۲, UCP۳, BNP, Caspase۳, and GAPDH) using real-time RT-PCR were performed. Results: Compared with the sham-operation group, the BDL group showed a significant rise in liver enzymes of AST, ALT, GGT, LDH, and ALP. Defined fibrotic and necrotic bundles and thick reticulin fibers were also found in BDL liver tissue. Besides liver morphological alterations, left ventricles of BDL ones were also associated with defined cardiomyocyte hypertrophy, myofiber vacuolization, and clear pigmentation. Findings showed a significant up-regulation of cardiac Brain Natriuretic Peptide (BNP) along with marked down-regulation in hepatic FXR, cardiac FXR, and cardiac UCP۲ and UCP۳. However, the expression of caspase ۳ in the cardiac tissue was not affected by BDL operation during ۴ weeks. Conclusion: Expression of FXR as an upstream regulator of cellular redox status, besides the non-enzymatic ROS buffering defense system of cardiac UCPs, has a pivotal role in the pathogenesis of cirrhotic-induced cardiac abnormality in rats.

Keywords:

Cardiomyopathy , cholestasis , Farnesoid-X-receptor , Liver Cirrhosis , Mitochondrial uncoupling proteins