Role of nitric oxide, nitroxidative and oxidative stress in wound healing.

Redox-regulated processes are relevant to wound healing. A balance between bioavailable nitric oxide (NO) concentration and a level of oxidative and nitroxidative stress in wounds may be crucial in wound repair. The highly beneficial effect of bioavailable NO is attributed to scavenging of superoxide, which is the main component of oxidative stress. Also, the high level of NO can influence angiogenesis and endothelial/skeletal muscle cell remodeling and proliferation. However, under conditions of excessive and prolonged production of O(2)(-) in wounds, the supplementation of NO can be evolved in significant increase in nitroxidative stress due to production of peroxynitrite (ONOO(-)) and peroxynitrous acid (ONOOH). ONOOH can trigger a cascade of events leading to the generation of highly reactive and damaging radicals and oxidative species. These species (mainly CO(3)(.-), NO(2)(+), NO(2), N(2)O(3), OH(.)) can impose significant damage in biological milieu and impair the process of wound healing. Therefore, a general strategy for an acceleration of the wound healing process may include an intervention(s) leading to the decrease in oxidative stress (treatment with antioxidants and/or prevention of O(2)(-) generation by uncoupled constitutive nitric oxide synthase, cNOS) and delivery of NO (treatment with NO donors, cNOS gene therapy). Here we briefly review the role of NO, and focus on O(2)(-) and ONOOH (major components of oxidative and nitroxidative stress respectively) in the normal and impaired process of wound healing.