Interrelation of liver vascularity to non-alcoholic fatty liver through a comparative study of the vasodilator effect of carvedilol or nicorandil in rats

Aim: An experimental study of the effect of two vasodilators, carvedilol (B blocker with alpha-antagonist) and nicorandil (NO donor) on nonalcoholic fatty liver (NAFLD) induced by hypercholesterolemia and fatty diet in rats through studying the possible anti-inflammatory and antioxidant mechanisms. Main methods: The rats were divided into 4 groups (6 rats each): The first (negative control group). The second, third and fourth groups were fed with cholesterol and fat- enriched diet for one month that stopped and continued on the standard diet for another month without treatment in the second group but treated with carvedilol and nicorandil in the third and fourth group respectively. Key findings: They revealed that both improved NAFLD especially nicorandil treated proved by the reduction of liver enzymes (AST, ALT), the fatty infiltration determined histologically and biochemically (decrease liver triglycerides). This may be due to either being antioxidants (reduced malondialdehyde and elevated reduced glutathione) or anti-inflammatory (decreased of TNF-alpha) together with the reduction of insulin resistance and adiponectin elevation or gene expression (increased liver NF-kappa B and decreased eNOS expression) and finally maybe by their obvious effect on improvements of lipid parameters. Significance: Carvedilol and nicorandil improved NAFLD through the interrelationship between inflammatory cytokines, antioxidants and insulin resistance.