Abstract
Melatonin (N-acetyl-5-methoxytryptamine) has been shown to have a cardioprotective effect against myocarditis. However, the mechanisms underlying the protective role of melatonin (MLT) in sepsis-induced myocarditis are yet to be revealed. In this study, MLT was administrated to mice, 14 days before cecal ligation puncture surgery. Echocardiography results showed that MLT alleviated cardiac dysfunction in sepsis-induced myocarditis. Furthermore, MLT reduced cardiac inflammation by inhibiting the expression of Il-1α, Il-1β, Il-6, and Mcp-1 messenger RNA (mRNA) levels. The RNA sequencing (RNA-seq) assays with heart tissues showed that MLT maintains the mitochondrial function in sepsis-caused myocarditis. Additionally, the production of reactive oxygen species (ROS) in heart tissues was suppressed by MLT. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced myocarditis, the results showed that MLT alleviated cardiac damage by regulating mitochondrial function and mitochondrial ROS.
Highlights
Sepsis represents a syndrome of physiologic, pathologic, and biochemical abnormalities caused by a systemic response to infection, which can result in dysfunctions of the lung, brain, liver, kidney, and heart [1, 2]
MLT significantly improved cardiac function marked by the recovery of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular end-systolic diameter (LVIDs) (Figures 1A–D)
Hematoxylin and eosin staining the sections from the heart tissues showed that the cecal ligation puncture (CLP) group exhibited a significant level of inflammatory cell infiltration and MLT protected the heart from inflammation damage (Figure 1E)
Summary
Sepsis represents a syndrome of physiologic, pathologic, and biochemical abnormalities caused by a systemic response to infection, which can result in dysfunctions of the lung, brain, liver, kidney, and heart [1, 2]. Myocarditis is a common complication that accounts for deaths in patients with sepsis, and its incidence is increasing yearly. Sepsis-induced myocarditis is present in half of all the patients with septic shock [3] and is characterized by the significant impairment of the left ventricular (LV) systolic and diastolic function [4]. Myocarditis is an independent prognostic risk factor for septic patients. Because of the shortage of therapeutic strategies for sepsis-induced myocarditis, effective prevention is especially critical. Mitochondrial dysfunction is involved in the pathogenesis of sepsis, Melatonin Alleviates Sepsis-Caused Myocarditis and the subsequent generation and accumulation of reactive oxygen species (ROS) are associated with the development of mitochondrial dysfunction. There are still no effective pharmacological strategies to treat or even reverse sepsis-induced myocarditis
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