Melatonin attenuates homocysteine-induced injury in human umbilical vein endothelial cells.

Homocysteine (Hcy) is a major risk factor for vascular disease and is closely associated with endothelial dysfunction. Melatonin is a neurohormone that is mostly produced by the pineal gland. Studies have reported that melatonin exhibits neuroprotective effects in several neurodegenerative disorders. The aim of the current study was to investigate the possible protective effect of melatonin against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanisms. HUVECs were exposed to Hcy in the presence or absence of melatonin. The effect of melatonin on viability was examined by MTT assay. Intracellular reactive oxygen species (ROS) levels were determined by 2',7'-dichlorofluorescein diacetate (DCF-DA). Further, expression of Bax, Bcl-2, and caspase-3 was analyzed by Western blot analysis. Lipid peroxidation (LPO) levels, total antioxidant power (TAP), and total thiol molecules were also evaluated. The results of this study revealed that melatonin significantly prevented Hcy-induced loss in cell viability in HUVECs. It was found that ROS significantly increased in the presence of Hcy, whereas melatonin reduced ROS production. Melatonin also downregulated Bax, upregulated Bcl-2, and decreased the expression and activity of caspase-3. Hcy increased the levels of LPO, and this effect was significantly attenuated by melatonin. Melatonin also increased the levels of TAP and total thiol molecules. It was concluded that melatonin played a protective role against Hcy-induced endothelium cell apoptosis through inhibition of ROS accumulation and the mitochondrial-dependent apoptotic pathway.