<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>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.</p></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.

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Department of Physiology, Military Medical Faculty, Gulhane Military Medical Academy, Ankara, Turkey

Department of Pharmacology, Military Medical Faculty, Gulhane Military Medical Academy, Ankara, Turkey

Interdisciplinary Toxicology

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great...

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Published Online: Jan 06, 2010

Page range: 219 - 228

DOI: https://doi.org/10.2478/v10102-009-0020-4

Keywords
antioxidants, cytokines, epigenetic, nitrosative stress, oxidative stress, peroxynitrite

This content is open access.

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Published Online: Jan 06, 2010

Page range: 219 - 228

DOI: https://doi.org/10.2478/v10102-009-0020-4

Keywordsantioxidants, cytokines, epigenetic, nitrosative stress, oxidative stress, peroxynitrite

This content is open access.

Keywords
antioxidants, cytokines, epigenetic, nitrosative stress, oxidative stress, peroxynitrite