Thymoquinone regulates nitric oxide synthase enzymes and receptor-interacting serine-threonine kinases in isoproterenol-induced myocardial infarcted rats.

This study aims to investigate the protective effects of thymoquinone (THQ) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Thirty-two rats were divided into four equal groups. Control, THQ; Intragastric(ig) by dissolved 20 mg/kg in 500 μl olive oil at 24-h intervals for 7 days, ISO; On the 6th and 7th days of the experiment, it was dissolved in 1 ml distilled water, 100 mg/kg, subcutaneously(sb), THQ + ISO; THQ was given 20 mg/kg at 24-h intervals for 7 days, 100 mg/kg was given on days 6 and 7 of the ISO experiment. At the end of the experiment, blood and heart tissues were taken and histological, Western blot and biochemical analyzes were performed. In the ISO group, cardiomyocyte damage and large necrotic areas were observed. While neuronal nitric oxide synthase (nNOS) decreased, inducible NOS (iNOS) and endothelial NOS (eNOS) expression increased. Receptor-interacting serine-threonine kinase (RIP/RIPK) RIP1 and RIP3 protein levels were increased. Lactate dehydrogenase (LDH), creatin-kinase (CK-MB) and cardiac troponin I (cTn-I) levels were increased. Atrial natriuretic peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were decreased. THQ caused the reduction of necrotic areas caused by ISO. NOS regulated enzyme levels. Increased ISO-induced decreased RIP1 and RIP3 expressions. THQ regulated the biochemical parameter levels. ISO triggers MI-induced necrosis through NOS enzymes by causing severe histological changes in heart tissue. THQ, on the other hand, reveals that it can be an important antinecrotic agent in the prevention of MI-induced damage by regulating both NOS enzyme levels and necrosis markers.