**5.2 Free radical cause peroxynitrites**

Physiological role for ONOO▬ as a down-modulator of immune responses and also as key mediator in cellular and tissue injury is associated with chronic activation of the immune system [93]. In chronic inflammatory diseases, peroxynitrite formed by phagocytic cells may cause damage to DNA which acts as epitopes for the production of autoantibodies [94]. The central role of peroxynitrite is performed in the control of infections in macrophages [95]. They are produced throughout the vascular system, regulate differentiation and contractility of vascular smooth muscle cells, control vascular endothelial cell proliferation and migration, mediate

platelet activation and hemostasis, and significantly contribute to the immune response [96]. Elevated reactive oxygen and nitrogen species are reduced levels of glutathione with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines [97]. The ONOO▬ could be modified by the histone proteins that lead to formation of oxidatively nitrated histones in the initiation and progression of autoimmune inflammatory diseases [98]. Peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens [99]. Being a mediator of protein oxidation and nitration, lipid peroxidation, mitochondrial dysfunction, and cell death, peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens [99].
