title: Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity.
abstract: Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production.
authors.affiliation: Department of Physiology, Military Medical Faculty, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Sukru
authors.initials: S
authors.lastname: Oter
authors.forename: Melik
authors.initials: M
authors.lastname: Seyrek
authors.forename: Turgut
authors.initials: T
authors.lastname: Topal