The Role of Nitric Oxide Donors in Wound Healing in Diabetes Mellitus

Diabetic foot ulcer is a serious complication of diabetes mellitus; it consists of lesions in the deep tissues associated with neurological disorders and peripheral vascular disease in the lower limbs. Delayed wound healing in diabetes leads to long-term hospitalization and even amputation of distal organs. Diabetes mellitus is associated with decreased nitric oxide bioavailability that causes dysfunction of the skin. Nitric oxide, a short-lived free radical, is produced in the skin, where it has important physiological functions. Much evidence suggests that nitric oxide accelerates wound healing. This review describes the pathways of nitric oxide production in the skin as well as role of nitric oxide donors in diabetic wound healing. Increased oxidative stress and arginase activity contribute to decreased nitric oxide bioavailability in diabetes. Based on data available, nitric oxide donors such as nitrite increase nitric oxide levels in the diabetic wound and improve would healing. It seems that increased nitric oxide in diabetic patients improves wound healing by increased collagen deposition and keratinocytes proliferation in the wound edges there by increasing reepithelialization capacity, chemoattractant of cytokines, increased formation of small blood vessels and increased blood flow to the wound site. In conclusion, nitric oxide donors could be considered as a potential and cost-effective treatment for diabetic wounds.