The role of nitric oxide in diabetic skin (patho)physiology

Abstract

The role of nitric oxide ([rad]NO) in cutaneous physiology/pathology became a growing research field since the discovery that almost all types of skin cells can synthetize this redox signaling molecule about 20 years ago. Now, it is evident that [rad]NO is an important player in skin physiological processes and in responses of cutaneous cells to external insults, while the impaired [rad]NO signaling has an important consequence in skin pathology. Skin disorders are common complications in diabetic conditions. Various metabolic/biochemical and immunological dysregulations in diabetic skin are tightly coupled with the disturbances in the redox state, primarily the ratio between [rad]NO and superoxide (О2[rad]−). This review describes possible therapeutic significance of different redox state modulators in the treatment of diabetic skin disorders. The focus is on those modulators that tightly control [rad]NO/О2[rad]− ratio through the complex mechanisms affecting endogenous [rad]NO and О2[rad]− producing and removing systems. The fact that classic antioxidants failed to show significant benefits in diabetes, emphasizes the importance of such redox mechanism-based and targeted approaches.