Role of nitric oxide in mediating the cardioprotective effect of agomelatine against isoproterenol-induced myocardial injury in rats
| Autor: | Ahlam M. Abdalla, Hanaa Mohamed Khalaf, Asmaa Mohamed Abdel-Aziz, Amira F. Ahmed |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cardiotonic Agents Arginine Myocardial Infarction Pharmacology medicine.disease_cause Nitric Oxide Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Acetamides Medicine Animals Myocardial infarction Rats Wistar Melatonin receptor agonist biology business.industry Myocardium Isoproterenol General Medicine medicine.disease Atenolol Rats Nitric oxide synthase Oxidative Stress 030104 developmental biology chemistry Apoptosis NADPH Oxidase 2 biology.protein business 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 393(10) |
| ISSN: | 1432-1912 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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