Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes

Abstract

Background: Melatonin (MT) has been shown to protect against various cardiovascular diseases. However, the effect of MT on lipopolysaccharide (LPS)-induced myocardial injury is poorly understood. This study aims to evaluate the effects of MT on LPS-induced myocardial injury in vitro.Methods: H9C2 cells were divided into a control group, MT group, LPS group, and MT + LPS group.The control group was treated with sterile saline solution, the LPS group received 8 μg/mL LPS for 24 h, MT + LPS cells were pretreated with 200 μmol/L MT for 2 h then with 8 μg/mL LPS for 24 h, and the MT group received only 200 μmol/L MT for 2 h. The CCK-8 assay and lactate dehydrogenase (LDH) activity assay were used to analyze cell viability and LDH release, respectively. Intracellular reactive oxygen species (ROS) and the rate of pyroptosis were measured using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and propidium iodide (PI) staining, respectively. The cell supernatants were used to measure the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1β by enzyme-linked immunosorbent assay (ELISA). The protein levels of iNOS, COX-2, NF-κB, p-NF-κB, NLRP3, caspase-1, and GSDMD were detected by western blot.Results: MT pretreatment significantly improved LPS-induced myocardial injury by inhibiting inflammation and pyroptosis in H9C2 cells. Moreover, MT inhibited the activation of the NF-κB pathway, and reduced the expression of inflammation-related proteins (iNOS and COX-2), and pyroptosis-related proteins (NLRP3, caspase-1, and GSDMD).Conclusions: Our data suggests that MT can alleviate LPS-induced myocardial injury, providing novel insights into the treatment of sepsis-induced myocardial dysfunction.

Anti‐PANoptosis is involved in neuroprotective effects of melatonin in acute ocular hypertension model

“…Besides, double immunofluorescence staining revealed that both NLRP3 and IL‐1β were expressed within microglia/macrophage population. Additionally, our findings were in line with previous studies, demonstrating the suppressive effect of melatonin on lipopolysaccharide (LPS)‐induced microglia pyroptosis, 104 cerebral ischemia‐induced pyroptosis, 105 LPS‐induced adipocyte pyroptosis, 106 and LPS‐induced cardiomyocyte pyroptosis 107 . Here, this study confirmed that melatonin prevented microglia/macrophage pyroptosis induced by AOH.…”

The role of ROS-induced pyroptosis in CVD

“…Melatonin (MT) has been proven to prevent a variety of cardiovascular diseases ( 33 ). In a study on the effect of MT on LPS-induced myocardial injury in vitro , it was found that MT could inhibit the inflammation and pyroptosis of H9C2 cells and significantly improve LPS-induced myocardial injury ( 52 ). Intracellular ROS were detected using the fluorescent probe DCFH-DA, and ROS were significantly decreased in the MT + LPS group.…”

The Role of Melatonin in Chronic Kidney Disease and Its Associated Risk Factors: A New Tool in Our Arsenal?

“…MT may mediate anti-inflammatory effects through nuclear factor (erythroid-derived 2)-like 2 activation, leading to inhibition of nuclear factor-kappaB and NLRP3 inflammasome activation pathways [13, 14]. Those additional MT effects could ameliorate endothelial cell function [15], which is negatively influenced by inflammatory stimuli [16].…”