Zinc deficiency exacerbates pressure ulcers by increasing oxidative stress and ATP in the skin.

BACKGROUND: Zinc deficiency is believed to be a predisposing factor for the development and intractable healing of pressure ulcers (PUs); however, the mechanisms of this association have not been elucidated. OBJECTIVE: Objective was to elucidate the mechanisms of the formation of severe and prolonged PUs under the zinc deficiency condition. METHODS: We assessed PUs formation after cutaneous ischemia-reperfusion (I/R) injury in mice fed with a zinc-adequate (ZA) or a zinc-deficient (ZD) diet from 2 weeks before I/R injury. Wound size, vascular damage, apoptotic cells, adenosine triphosphate (ATP) amount, and the number of Langerhans cells (LCs) in I/R area were analyzed. We evaluated the extent of oxidative stress in I/R area in OKD48 mice through bioluminescence detection. RESULTS: We found that dietary zinc deficiency caused the formation of severe and prolonged PUs in mice. Zinc deficiency increased the vascular disorder, oxidative stress, and apoptosis induced by cutaneous I/R injury. I/R injury-induced oxidative stress signals were significantly higher in ZD OKD48 mice than in ZA OKD48 mice. Additionally, zinc deficiency reduced the number of LCs and increased the amount of ATP in cutaneous I/R-injured skin. Oral supplementation of zinc improved zinc deficiency-associated PUs. CONCLUSION: Zinc deficiency might increase cutaneous I/R injury-induced vascular damages, oxidative stress, and apoptosis, as well as ATP amount in I/R area due to the loss of LCs. These mechanisms might partly account for zinc deficiency-induced formation of severe and prolonged PUs. Oral supplementation of zinc might be a reasonable therapeutic choice for patients with PUs and zinc deficiency.