Effect of nebivolol on altered skeletal and cardiac muscles induced by dyslipidemia in rats: impact on oxidative and inflammatory machineries.

AIM: High cholesterol diet is greatly linked to deleterious health consequences. In this work we tried to explore direct effects of high cholesterol diet on striated (skeletal and cardiac) muscle tissues and the mechanisms by which nebivolol could improve such harmful effects. METHODS: The study included 24 healthy adult male albino rats weighing 200-220 grams that were assigned into four groups: control group, control drug group, high cholesterol diet fed groups; one untreated the other was treated with nebivolol. RESULTS: In the cholesterol fed group, we found decreased blood HDL and NO with elevated total cholesterol, triglycerides, myoglobin, CK, LDH, ALP, in addition to elevated muscle tissue levels of HIF-1, NF-kB, MDA, and decreased expression of both eNOS, reduced GSH. Wire hanging test time was shorter in the high cholesterol group than control group rats, which was confirmed histologically by increased striated muscle fibre thickness and cytochrome area %. Nebivolol treatment ameliorated the effects of high cholesterol diet. CONCLUSION: High cholesterol diet caused myopathic changes in rat striated muscle tissues mostly due to oxidative stress associated with enhanced NF-kB and HIF-1 expression. Nebivolol appears beneficial in the management of hypercholesterolaemia-induced striated muscle injury.

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-α) together with the reduction of insulin resistance and adiponectin elevation or gene expression (increased liver NF-κB 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.