Melatonin as a promising agent alleviating endocrine deregulation and concurrent cardiovascular dysfunction: a review and future prospect

Abstract

Endocrine modulation of various growth and survival mechanisms is at the helm of cellular homeostasis and impaired endocrine balance may potentially galvanize cardiovascular health to go haywire. Melatonin, an effective antioxidant and multipotent hormone has preponderant influence on the activities of several endocrine factors including growth hormones, thyroid hormones, gastro-intestinal hormones, and those controlling reproductive and metabolic functions. Many of these hormones tightly regulate cardiovascular functions while the mammalian heart has its own endocrine machinery. Endocrine disruptions severely affect cardiovascular integrity and hormonal therapies may instigate adverse cardiac events. Therefore, this review focuses on the cardioprotective potential of melatonin concerning endocrine instability-mediated cardiovascular dysfunction. Melatonin has been reported to effectively counteract sympathetic overstimulation and also reduce the cardiotoxic attributes of catecholamines and their derivatives. Melatonin suppresses the pernicious cardiovascular manifestation of thyrotoxicosis and autoimmune thyroiditis, which is possibly attributed to its antioxidant property and regulation of iodothyronine-deiodinase activity. Interestingly, being a circadian synchronizer melatonin potentially preserves the diurnal pattern of insulin secretion and thereby improves glucose tolerance and cardiac GLUT-4 expression. Besides, melatonin modulates insulin signaling pathway by enhancing the activation of insulin receptor-associated tyrosine kinase, thus protecting the heart against diabetogenic outcomes. Further, melatonin has demonstrated its beneficial action against non-dipper hypertension by regulating the RAAS function. However, there is a plethora of unresolved research question that necessitates additional investigation into the potential therapeutic effect of melatonin in endocrine dysfunctions that emanates during various physiological and pathological states and may have potentially harmful cardiovascular implications.