Effects of melatonin on apoptosis, necroptosis and pyroptosis in myocardial ischemia reperfusion injury; role of asprosin

Our study aimed to investigate the role of apoptosis, necroptosis and pyroptosis in myocardial ischemia reperfusion (IR) injury and to investigate the effects of melatonin on these cell death pathways and asprosin levels. For this purpose, apoptotic protease activating factor-1 (APAF1), which plays a central role in apoptosis, serine/threonine-protein kinase 3 (RIPK3), which is involved in necroptosis, intracellular signaling protein, gasdermin D (GSDMD), which plays a role in pyroptosis, and asprosin, a peptide adipokine secreted by white adipose tissue, were examined. 42 male Sprague Dawley rats weighing 300-320 g were used. IR was applied to the left coronary artery as 30 minutes of ischemia and 120 minutes of reperfusion. Melatonin and solvent were given intravenously by injection from the jugular vein with an infusion pump after occlusion during reperfusion. Electrocardiography, blood pressure and heart rate were recorded throughout the experiment. Cardiac tissue APAF1, RIPK3 and GSDMD levels were analyzed by Western Blot and serum asprosin levels were analyzed by enzyme-linked immunosorbent assay (ELISA) method. APAF1, RIPK3 and GSDMD protein expression levels were significantly increased by IR and significantly decreased by melatonin. Serum asprosin levels were decreased by IR and increased by melatonin administration. Apoptosis, necroptosis and pyroptosis may play a role in the pathophysiology of myocardial IR injury. Melatonin may reduce myocardial IR injury by decreasing APAF1/RIPK3/GSDMD pathways and increasing asprosin levels.