Melatonin as a protective agent in cardiac ischemia-reperfusion injury: Vision/Illusion?

Melatonin, an emphatic endogenous molecule exerts protective effects either via activation of G-protein coupled receptors (Melatonin receptors, MTR 1-3), tumor necrosis factor receptor (TNFR), toll like receptors (TLRS), nuclear receptors (NRS) or by directly scavenging the free radicals. MTRs are extensively expressed in the heart as well as in the coronary vasculature. Accumulating evidences have indicated the existence of a strong correlation between reduction in the circulating level of melatonin and precipitation of heart attack. Apparently, melatonin exhibits cardioprotective effects via modulating inextricably interlinked pathways including modulation of mitochondrial metabolism, mitochondrial permeability transition pore formation, nitric oxide release, autophagy, generation of inflammatory cytokines, regulation of calcium transporters, reactive oxygen species, glycosaminoglycans, collagen accumulation, and regulation of apoptosis. Convincingly, this review shall describe the various signaling pathways involved in salvaging the heart against ischemia-reperfusion injury.