Biochemical and cellular toxicology of peroxynitrite: implications in cell death and autoimmune phenomenon

Reactive nitrogen species include nitric oxide (center dot NO), peroxynitrite (ONOO-) and nitrogen dioxide radical (NO2 center dot). Peroxynitrite is a reactive oxidant, produced from nitric oxide (center dot NO) and superoxide anion (O-2(center dot-)), that reacts with a variety of biological macromolecules. It is produced in the body in response to physiological stress and environmental toxins. It is a potent trigger of oxidative protein and DNA damage-including DNA strand breakage and base modification. It activates the nuclear enzyme poly-ADP ribose polymerase (PARP) resulting in energy depletion and apoptosis/necrosis of cells. Peroxynitrite generation is a crucial pathological mechanism in stroke, diabetes, inflammation, neurodegeneration, cancer, etc. Peroxynitrite modified DNA may also lead to the generation of autoantibodies in various autoimmune disorders such as systemic lupus erythematosus (SLE). In chronic inflammatory diseases, peroxynitrite formed by phagocytic cells may cause damage to DNA, generating neoepitopes leading to the production of autoantibodies. Hence, understanding the pathophysiology of peroxynitrite could lead to important therapeutic interventions.