Role of nitric oxide in mediating the cardioprotective effect of agomelatine against isoproterenol-induced myocardial injury in rats.
2020
: Myocardial infarction (M/I) is a common cause of mortality worldwide. Agomelatine (AGO), a potent melatonin receptor agonist, proved to have an anti-inflammatory and antioxidant effect. The present study aimed to explore the cardioprotective effect of AGO on isoproterenol (ISO)-induced myocardial injury in a rat model and determine the role of nitric oxide (NO) in mediating this beneficial effect. Rats were randomly divided into 6 groups and treated for 12 days. Group 1, control, received normal saline. Group 2, ISO group, received ISO (100 mg/kg, i.p.) in 11th and 12th days. Group 3, positive control group, received atenolol (100 mg/kg/day) + ISO. Group 4, AGO-treated group, received AGO (80 mg/kg/day) + ISO. Group 5, L-NNA + ISO, received L-NG-nitro arginine (L-NNA) (25 mg/kg, orally) + ISO. Group 6, AGO + L-NNA + ISO, co-treated with AGO + ISO + L-NNA. Serum cardiac enzymes and cardiac tissue oxidative stress parameters were assessed along with histopathological evaluation. Gene expression quantification of nuclear factor erythroid 2 (Nrf-2) and heme oxygenase-1 (HO-1) were assessed. Immunoexpression of inducible NO synthase (iNOS) and caspase-3 were evaluated. The outcomes proved that ISO significantly increased serum cardiac enzymes, with histopathological changes of myocardial tissue along with a major increase in oxidative, inflammatory, and nitrosative stress, besides a reduction in cardiac Nrf-2 and HO-1 gene expressions with marked myocardial cell apoptosis. However, pretreatment with AGO significantly reversed these profound ISO myocardial damaging effects. AGO protects against ISO-induced myocardial injury through its antioxidant, anti-inflammatory, and anti-apoptotic effects with modulation of NOS enzymes.
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