Influence of tissue nitration on tissue damage with thermal injury

A gas mediator, nitric oxide, is converted into peroxynitrite in the presence of superoxide anion. Peroxynitrite is a potent oxidant, which injures various tissues and organs by nitration of tyrosine residue in protein and enhances the inflammatory response in the prolonged phase. In this study, the authors investigated the relationship between peroxynitrite-mediated tissue nitration and tissue damage with thermal injury using an experimental burn model. The content of nitrotyrosine in the burned tissue significantly increased 1 to 6 h after injury. The nitrotyrosine content in the burned ear significantly decreased with 100 mg/kg of LNAME administration. Vascular hyperpermeability was also significantly suppressed in the iNOS antibody immunoneutralized mice 6 h after injury. There was a positive correlation between the severity of tissue damage, an indicator of which is the increase in the weight of the burned ear along with the development of edema after injury, and the concentration of nitrotyrosine in the wound tissues. Nitrotyrosine-like immune reactants were also diffusely detected in the burned region and the surrounding areas. These results indicate that peroxynitrite is produced in the surrounding burned region and a reaction of nitration of tissue tyrosine is involved with tissue damage at the burn wound. Therefore, to prevent the systemic vascular hyperpermeability and tissue damage in a large area burn or severe burn patients, the administration of NOS inhibitors or radical erasers may be easy to manage generally by inhibition of peroxynitrite formation.