Protective effects of melatonin against hypoxia-induced TM۳ cell damage via suppression of the TGF-β pathway

This study aimed to explore whether melatonin protects TM۳ Leydig cells from cobalt (II) chloride (CoCl۲)-induced hypoxia through the transforming growth factor beta (TGF-β) signaling pathway. Cells were divided into four groups: a control group without treatment (Group ۱), a melatonin group (۱۰.۰۰ ng mL-۱; Group ۲), a group treated with CoCl۲ (۱۰۰ µM) to induce hypoxia (Group ۳), and a melatonin + CoCl۲ group (Group ۴). After ۹۶ hr of incubation, cell viability was assessed using the MTT assay, and transforming growth factor beta ۱, activin receptor-like kinase-۵, and bone morphogenetic protein ۴ gene and protein expressions were measured through RT‑PCR and western blotting. The CoCl۲ and melatonin + CoCl۲ groups exhibited significantly diminished cell viability compared to the control. However, melatonin treatment enhanced survival in the CoCl۲-exposed cells. Notably, transforming growth factor beta ۱ expression was elevated in all groups. Activin receptor-like kinase-۵ (gene and protein expression increased in CoCl۲-treated groups but was lower in the melatonin + CoCl۲ group. Melatonin treatment reduced bone morphogenetic protein ۴ expression compared to the control, while CoCl۲ groups showed increased bone morphogenetic protein ۴ levels. These findings suggest melatonin's potential as a therapeutic agent against oxidative stress and hypoxia in TM۳ cells through its antioxidant properties.

کلیدواژه ها:

Cobalt (II) chloride ، Leydig cells ، Melatonin ، TGF-&beta ، Signaling Pathway