Cardioprotective effects of melatonin in vitro and in two in vivo models of heart disease: Isoproterenol-induced cardiac injury and pulmonary hypertension.

Several studies have shown that melatonin is a promising therapeutic strategy for the treatment of cardiac diseases. However, no studies have compared the effects of this hormone in different experimental models of heart injury. Therefore, the aim of the present study was to evaluate the effects of melatonin in three different experimental models of cardiac disease: one in vitro model (H9c2 cells exposed to H2O2) and two in vivo models of heart disease (isoproterenol-induced cardiac injury and monocrotaline-induced pulmonary arterial hypertension). The main findings of the in vitro protocol were that pre-treatment with melatonin improved the viability of H9c2 cells exposed to H2O2 and partially prevented the decrease in cellular antioxidant defences. In the isoproterenol-induced cardiac injury model, melatonin administration improved left ventricular function and prevented the decrease in ventricular diameters. In addition, melatonin decreased NLRP3 expression. In the PAH model, melatonin prevented the decrease in pulmonary artery diameter and improved RV function. In addition, this hormone decreased xanthine oxidase expression. In conclusion, melatonin showed similar cardioprotective effects in all experimental models used, improving cell survival and functional parameters of both ventricles. The cardioprotective effects of melatonin may be associated with changes in protein expression in the two in vivo models evaluated. However, mechanistic conclusions remain hypothetical. These data reinforce the therapeutic potential of melatonin for the heart under different pathological conditions.