Melatonin: A potential protective multifaceted force for sepsis-induced cardiomyopathy

Sepsis is a life-threatening condition manifested by organ dysfunction caused by a dysregulated host response to infection. Lung, brain, liver, kidney, and heart are among the affected organs. Sepsis-induced cardiomyopathy is a common cause of death among septic patients. Sepsis-induced cardiomyopathy is characterized by an acute and reversible significant decline in biventricular both systolic and diastolic function. This is accompanied by left ventricular dilatation. The pathogenesis underlying sepsis-induced cardiomyopathy is multifactorial. Hence, targeting an individual pathway may not be effective in halting the extensive dysregulated immune response. Despite major advances in sepsis management strategies, no effective pharmacological strategies have been shown to treat or even reverse sepsis-induced cardiomyopathy. Melatonin, namely, N-acetyl-5-methoxytryptamine, is synthesized in the pineal gland of mammals and can also be produced in many cells and tissues. Melatonin has cardioprotective, neuroprotective, and anti-tumor activity. Several literature reviews have explored the role of melatonin in preventing sepsis-induced organ failure. Melatonin was found to act on different pathways that are involved in the pathogenesis of sepsis-induced cardiomyopathy. Through its antimicrobial, anti-inflammatory, and antioxidant activity, it offers a potential role in sepsis-induced cardiomyopathy. Its antioxidant activity is through free radical scavenging against reactive oxygen and nitrogen species and modulating the expression and activity of antioxidant enzymes. Melatonin anti-inflammatory activities control the overactive immune system and mitigate cytokine storm. Also, it mitigates mitochondrial dysfunction, a major mechanism involved in sepsis-induced cardiomyopathy, and thus controls apoptosis. Therefore, this review discusses melatonin as a promising drug for the management of sepsis-induced cardiomyopathy. Protective actions of melatonin against Sepsis-induced Cardiomyopathy (SIC). BAP31/ERK, extracellular-signal-regulated kinase-B cell receptor-related protein 31; CAT, catalase; GSH, Glutathione; GST, Glutathione S-transferase; GPx, Glutathione Peroxidase; MCP1, Monocyte Chemoattractant protein1; NET, neutrophil extracellular trap; NLRP3, NOD-like receptor protein 3; NRF2, nuclear factor E2-related Factor 2; NO, Nitric Oxide Ripk3, receptor-receptor-interacting protein kinase 3; ROS, Reactive Oxygen Species; SOD, Superoxide dismutase. [Display omitte