Hydrogen gas inhalation protects against cutaneous ischaemia/reperfusion injury in a mouse model of pressure ulcer

Pressure ulcer formation depends on various factors among which repetitive ischaemia/reperfusion(I/R) injury plays a vital role. Molecular hydrogen (H(2)) was reported to have protective effects on I/R injuries of various internal organs. In this study, we investigated the effects of H(2) inhalation on pressure ulcer and the underlying mechanisms. H(2) inhalation significantly reduced wound area, 8‐oxo‐dG level (oxidative DNA damage) and cell apoptosis rates in skin lesions. H(2) remarkably decreased ROS accumulation and enhanced antioxidant enzymes activities by up‐regulating expression of Nrf2 and its downstream components in wound tissue and/or H(2)O(2)‐treated endothelia. Meanwhile, H(2) inhibited the overexpression of MCP‐1, E‐selectin, P‐selectin and ICAM‐1 in oxidant‐induced endothelia and reduced inflammatory cells infiltration and proinflammatory cytokines (TNF‐α, IL‐1, IL‐6 and IL‐8) production in the wound. Furthermore, H(2) promoted the expression of pro‐healing factors (IL‐22, TGF‐β, VEGF and IGF1) and inhibited the production of MMP9 in wound tissue in parallel with acceleration of cutaneous collagen synthesis. Taken together, these data indicated that H(2) inhalation suppressed the formation of pressure ulcer in a mouse model. Molecular hydrogen has potentials as a novel and alternative therapy for severe pressure ulcer. The therapeutic effects of molecular hydrogen might be related to its antioxidant, anti‐inflammatory, pro‐healing actions.