Temporal effect of melatonin posttreatment on anoxia/reoxygenation injury in H9c2 cells

Abstract

Melatonin has been proven to reduce myocardial ischemia-reperfusion (MI/R) injury.However, in most studies, melatonin was administered before MI/R, thus, the results lack clinical significance in patients with acute myocardial infarction. We hypothesize that melatonin posttreatment at different times has different curative effects. Administered of Melatonin (150 μM) at different times after the onset of reoxygenation (t = −15, 0, 5, 10, 15, and 30 min). Cellular apoptosis, oxidative stress, and mitochondrial function were assessed. Mitophagy-related protein levels, mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) activity were also measured. A/R injury upregulated mitophagy, which was associated with increased cellular apoptosis, oxidative stress, and mitochondrial dysfunction. Melatonin posttreatment (t = −15, 0, 5, 10, 15, and 30 min) significantly inhibited excessive mitophagy after A/R injury, reduced cellular apoptosis and oxidative stress, restored mitochondrial function and MMP, and restrained mPTP opening. The therapeutic time window in which melatonin posttreatment protected H9c2 cells against A/R injury was large (from −15 to 30 min after the onset of reperfusion), but the earlier the melatonin administration was, the better its protective effect was. This mechanism is likely due to a reduction in mPTP activity and MMP collapse, which lead to the inhibition of mitophagy.

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

“…Antioxidant effects were reported in Sprague–Dawley rats with myocardial ischemia/reperfusion injury, where MT decreased cardiac malondialdehyde while increasing cardiac SOD and GPx by activating the JAK2/STAT3 signaling pathway [ 134 ]. Similar results have been documented in other preclinical studies of cardiac ischemia/reperfusion injury [ 135 , 136 , 137 , 138 ]. Activation of cardiac MT2, but not MT1 receptors, may be responsible for this effect [ 139 ].…”