There has been increasing evidence that cutaneous ischemia-reperfusion (I/R) injury is key player in the pathogenesis of the early stage of pressure ulcers (PUs). However, there is no effective treatment to prevent the development of ulcer formation in acute phase of PUs. Dimethyl fumarate (DMF) is FDA-approved drug for managing relapsing multiple sclerosis and psoriasis. DMF possesses therapeutic effects in animal models on fibrosis and ischemic disorders via enhancement of Nrf2 activity eliciting suppressing oxidative stress, and inhibition of inflammatory responses, suggesting that DMF may have potential to prevent the formation of PUs after cutaneous I/R injury. The objective of this study was to clarify the effect of orally administrated DMF on the formation of PUs by cutaneous I/R injury mice model and the mechanisms of the protective effect of DMF. We found that the administration of DMF after cutaneous I/R significantly inhibited the formation of PUs. Quantitative studies of immunofluorescence staining revealed that DMF treatment prevented the reduction of the number of blood vessels (CD31+ endothelial cells and αSMA+ pericytes), and suppressed the apoptosis in I/R site. qPCR examination revealed that mRNA levels of inflammatory cytokines (TNF-α and IL-6) expression were suppressed in I/R site by DMF treatment. Moreover, we proved antioxidative effect of administration of DMF on cutaneous I/R injury with OKD 48 (Keap1-dependent oxidative stress detector) mice, which enabled evaluating oxidative stress through bioluminescence detection. In an in vitro study, DMF treatment suppressed the production of reactive oxygen species in HUVECs. Collectively, we conclude that administration of DMF might have the therapeutic possibility for cutaneous I/R injury as translational target for new treatment of PUs.

Administration of dimethyl fumarate prevents the development of pressure ulcer formation after cutaneous I/R injury