Melatonin Modulates Oxidative Stress And Ferroptosis In Hpdlscs Via Sirt1

To explore how melatonin (MT) affects oxidative stress and ferroptosis in human periodontal ligament stem cells (hPDLSCs) within inflammatory microenvironment by regulating silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). hPDLSCs were cultured in vitro and divided into five groups:blank control group, LPS group, melatonin group, SIRT1 inhibition with melatonin group, and SIRT1 activation with melatonin group. Colorimetric assay kits measured intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and ferrous ion level. RT-qPCR and WB detected ferroptosis-related mRNA and protein expressions. Fluorescence microscopy observed reactive oxygen species (ROS) level and transmission electron microscopy (TEM) examined cell ferroptosis characteristics. Ferroptosis markers and ROS increased while negative regulatory and antioxidant factors decreased in the LPS group. Melatonin reversed these changes. SIRT1 inhibition with melatonin had adverse effects compared to control and melatonin groups. Under the TEM, LPS group and SIRT1 inhibition with melatonin group showed ferroptosis characteristics. SIRT1 and PGC-1α protein expression decreased in LPS group and SIRT1 inhibition with melatonin group accordingly. hPDLSCs experience oxidative stress and ferroptosis in the inflammatory microenvironment. Melatonin can inhibit these by regulating SIRT1 and its down-stream PGC-1α.