Protective effect of dimethyl fumarate for the development of pressure ulcers after cutaneous ischemia‐reperfusion injury

Abstract

Ischemia‐reperfusion (I/R) is associated with various pathogenic conditions, and there has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non‐blanchable erythema. Several studies demonstrated that oxidative stress is a key player in I/R injury, and the inhibition of oxidative stress may be capable of protecting tissue damage after I/R injury in various organs including skin. Dimethyl fumarate (DMF) approved by the Food and Drug Administration is Nrf2 activator, and recent studies revealed the antioxidative and anti‐inflammatory effects of DMF on I/R injury in animal models. Our objective was to assess the effects of oral administration of DMF on the development of PUs after cutaneous I/R injury in mice. We found that DMF administration significantly decreased the size of PUs after cutaneous I/R. Cutaneous I/R‐induced oxidative stress was also significantly inhibited by DMF in OKD48 mice, in which oxidative stress can be visually assessed. In addition, DMF treatment decreased hypoxic area, the numbers of apoptotic cells, and vascular loss in I/R area. DMF treatment suppressed the infiltration of MPO+ neutrophils and the production of proinflammatory cytokines in I/R site after cutaneous I/R injury. in vitro experiments, DMF treatment suppressed the production of reactive oxygen species in pericyte‐like cells. These results suggest that DMF treatment might prevent the formation of PUs induced by cutaneous I/R injury via suppressing oxidative stress and subsequent inflammation. DMF treatment during the early phase of decubitus ulcers might protect against further progression.

Effect of “micromovement” in preventing intraoperative acquired pressure injuries among patients undergoing surgery in supine position

“…On the one hand, localized tissue cells are subjected to the traction brought by prolonged and sustained pressure, leading to cell morphological and structural changes. While on the other hand, when local tissues underwent the vertical pressure that is higher than the normal capillary pressure of 16–32 mmHg for a long time, local blood flow may be blocked, resulting in microcirculatory disorders in the pressure‐bearing tissues or organs, ischemic–hypoxic injuries, and finally the development of PIs 7 . Besides, ischemia–reperfusion (I/R) has been proven to be the crucial mechanism underlying the development of PIs.…”

“…In the review criteria of tertiary general hospitals, IAPI is regarded as the key indicator evaluating clinical care quality, and research on current PI prevalence is taken as a link in continuous quality improvement 5 . In this context, IAPI prevention and the reduction of its incidence are highly valued, and numerous scholars have concentrated on the development and improvement of IAPI prevention measures 6,7 …”

“…5 In this context, IAPI prevention and the reduction of its incidence are highly valued, and numerous scholars have concentrated on the development and improvement of IAPI prevention measures. 6,7 Previous study anaesthesia duration (odds ratio [OR] 1.005) and total time of diastolic blood pressure <50 mmHg (OR: 1.007) were significantly associated with IAPI. 8 Skin surface temperature is another intrinsic factor related to PI.…”

Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone

“…Interestingly, administration of dimethyl fumarate leads to increased Nrf2 and HO-1 expression [ 122 ]. Dimethyl fumarate treatment also decreases cell injury during ischemia-reperfusion by increasing HO-1 expression [ 123 , 124 ]. Stimulation of HO-1 expression with dimethyl fumarate treatment may be a novel approach to decrease cell injury during aging because endogenous antioxidants are already impaired [ 121 ].…”

Dysfunctional iron metabolism in pressure injuries is related to aberrant CD163 and Homx‐1 signal transduction

“…DTPI is mainly caused by pressure‐driven local microcirculatory impairment and repetitive ischemia/reperfusion injury (IRI) 5,6 . IRI is one of the fundamental causes of cell death and organ damage, 7,8 mainly associated with oxidative stress.…”