Role of nitric oxide in mediating the cardioprotective effect of agomelatine against isoproterenol-induced myocardial in
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ORIGINAL ARTICLE
Role of nitric oxide in mediating the cardioprotective effect of agomelatine against isoproterenol-induced myocardial injury in rats Hanaa M. Khalaf 1 & Ahlam M. Abdalla 2 & Amira F. Ahmed 3 & Asmaa Mohamed Abdel-Aziz 1 Received: 30 October 2019 / Accepted: 24 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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, LNNA + 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 (HO1) 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 antiapoptotic effects with modulation of NOS enzymes. Keywords Agomelatine . Caspase . Myocardial injury . Nitric oxide synthase
Introduction Cardiovascular diseases (CVDs) are still leading causes of high morbidity and mortality despite of several new advancements in medical interventions. Ischemic heart diseases; acute myocardial infarction (M/I) in particular, is one of the most alarming CVDs (Barman et al. 2013) which resulted from the disturbed balance between the supply and the demand of the * Asmaa Mohamed Abdel-Aziz [email protected]; [email protected] 1
Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, Egypt
2
Department of Biochemistry, Faculty of Medicine, Minia University, Minia 61511, Egypt
3
Department of Histology, Faculty of Medicine, Minia University, Minia 61511, Egypt
blood. Although several mechanisms share in the pathogenesis of myocardial insufficiency, the putative roles of these processes remain elusive. Increasing evidence
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