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

Abstract

Using a mouse model of repetitive cutaneous ischaemia/reperfusion (I/R) injury that mimics pressure ulcer formation, this study examined the effects of molecular hydrogen (H2) gas inhalation. H2 inhalation significantly reduced wound area, oxidative DNA damage (8-oxo-dG levels), and apoptosis rates in skin lesions. ROS accumulation was suppressed while antioxidant enzyme activities were enhanced through upregulation of Nrf2 and its downstream components in wound tissue and H2O2-treated endothelial cells. Endothelial overexpression of MCP-1, E-selectin, P-selectin, and ICAM-1 was attenuated, and infiltration of inflammatory cells along with production of TNF-α, IL-1, IL-6, and IL-8 was reduced. Concurrently, pro-healing mediators including IL-22, TGF-β, VEGF, and IGF1 were upregulated, MMP9 production was suppressed, and cutaneous collagen synthesis was accelerated. These findings indicate that H2 inhalation suppresses pressure ulcer development through coordinated antioxidant, anti-inflammatory, and wound-healing mechanisms.

Mechanism

H2 activates the Nrf2 pathway to enhance antioxidant enzyme activity and reduce ROS, suppresses endothelial adhesion molecules (MCP-1, E-selectin, P-selectin, ICAM-1) and pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-8), upregulates pro-healing factors (IL-22, TGF-β, VEGF, IGF1), and inhibits MMP9 to promote collagen synthesis.