Protective Effects of Hydrogen Treatment Against High Glucose-Induced Oxidative Stress and Apoptosis via Inhibition of the AGEs/RAGE/NF-κB Signaling Pathway in Skin Cells

Background: Diabetic wounds are major clinical challenges, often complicated by oxidative stress and free radical generation. Hydrogen (H2), a selective antioxidant, offers potential as a therapeutic agent for chronic diabetic wounds. However, its precise mechanisms remain underexplored. Objective: This study aimed to investigate the protective effects of H2 on high glucose-induced oxidative damage and apoptosis in human skin cells. Methods: HaCaT keratinocytes and HSF fibroblasts were treated with high glucose or AGEs. Cell viability, oxidative stress markers, inflammatory cytokines, and apoptosis were analyzed. AGEs/RAGE/NF-κB signaling was evaluated via Western blot. Results: H2 treatment significantly reduced ROS, MDA, IL-1β, and TNF-α levels, while enhancing SOD and GSH activity. It also inhibited AGEs/RAGE/NF-κB signaling and apoptosis. Conclusion: Hydrogen therapy protects against oxidative stress and inflammation induced by high glucose or AGEs, offering potential as an adjunctive treatment for diabetic wound healing.