Melatonin may be associated with changes in HUWE1, AIM2 and PANoptosis‐related proteins following myocardial ischaemia–reperfusion in male rats

Abstract Melatonin secreted by the pineal gland is a neuroendocrine hormone that directly scavenges free radicals and activates receptor‐mediated signalling pathways in the cardiovascular system. This antioxidant molecule plays critical roles in processes such as limiting ischaemia–reperfusion (IR) damage, preventing apoptosis, correcting endothelial dysfunction and preventing myocardial remodelling. However, its role in multiple programmed cell death processes induced by IR remains uncertain. Understanding the role of PANoptosis, one of these processes, in myocardial IR damage and the effect of melatonin could lead to innovative treatment strategies. In this study, the aim was to investigate the effects of melatonin on myocardial IR damage, focusing on the levels of the mitophagy mediator HECT, UBA, and WWE domain‐containing E3 ubiquitin ligase 1 (HUWE1), PANoptosis proteins absent in melanoma 2 (AIM2), receptor‐interacting protein kinase 3 (RIPK3), and gasdermin D, as well as apoptotic protease‐activating factor 1 (APAF1) levels, and the levels of microRNA (miR)‐136 and ‐325 that may be associated with these proteins. Thirty minutes of ischaemia and 120 min of reperfusion were applied to the left coronary artery of the rats. Melatonin was administered at the beginning of reperfusion (10 mg/kg). Serum AIM2 and tissue HUWE1, RIPK3, gasdermin D and APAF1 levels were significantly increased whereas miR‐136 and miR‐325 levels were decreased; melatonin reversed these effects. The increase in serum AIM2 levels following IR damage and the decrease in these levels after melatonin administration suggest that serum AIM2 should be more thoroughly investigated as a potential biomarker for damage and treatment response.