Propofol attenuates H2O2-induced senescence in human umbilical vein endothelial cells by activating the NRF2/HO-1 axis.

This study investigated the protective effect and mechanism of propofol (PPF) against hydrogen peroxide (H2O2)-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). An H2O2-induced injury model was established and treated with various concentrations of PPF. The results demonstrated that PPF significantly alleviated H2O2-induced cytotoxicity, apoptosis, proliferative suppression, and cellular senescence while enhancing cell migration and tube formation. Mechanistically, PPF increased the activities of antioxidant enzymes (SOD, CAT, GSH-Px), reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, suppressed the release of inflammatory cytokines (IL-6, IL-8, TNF-α), promoted endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production, and maintained intracellular adenosine triphosphate (ATP) content. Under conditions of chronic, sustained oxidative stress, PPF remained effective in activating the NRF2/HO-1 pathway and alleviating cellular damage. Furthermore, PPF facilitated nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and up-regulated the expression of its downstream target heme oxygenase-1 (HO-1). Inhibition of NRF2 using ML385 significantly attenuated the antioxidant, anti-senescent, and cytoprotective effects of PPF. In conclusion, PPF mitigates H2O2-induced endothelial cell injury and functional impairment by activating the NRF2/HO-1 pathway and modulating the ROS-eNOS/NO-ATP axis, suggesting its potential as an endothelial protective agent in clinical settings.