Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications

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Main Author: Ohara Augusto
Format: Artículo científico
Language:en
Published: Academia Brasileira de Ciências 2008
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author Ohara Augusto
author_facet Ohara Augusto
contents Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications Ohara Augusto Daniel F. Trindade Edlaine Linares Sandra M. Vaz Multidisciplinaria (Ciencias Naturales y Exactas) tempol antioxidants nitric oxide inflammation derived oxidants The substantial therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) and related cyclicnitroxides as antioxidants has stimulated innumerous studies of their reactions with reactive oxygen species. In comparison,reactions of nitroxides with nitric oxide-derived oxidants have been less frequently investigated. Nevertheless,this is relevant because tempol has also been shown to protect animals from injuries associated with inflammatoryconditions, which are characterized by the increased production of nitric oxide and its derived oxidants. Here, wereview recent studies addressing the mechanisms by which cyclic nitroxides attenuate the toxicity of nitric oxidederivedoxidants. As an example, we present data showing that tempol protects mice from acetaminophen-inducedhepatotoxicity and discuss the possible protection mechanism. In view of the summarized studies, it is proposed thatnitroxides attenuate tissue injury under inflammatory conditions mainly because of their ability to react rapidly withnitrogen dioxide and carbonate radical. In the process the nitroxides are oxidized to the corresponding oxammoniumcation, which, in turn, can be recycled back to the nitroxides by reacting with upstream species, such as peroxynitriteand hydrogen peroxide, or with cellular reductants. An auxiliary protection mechanism may be down-regulation ofinducible nitric oxide synthase expression. The possible therapeutic implications of these mechanisms are addressed. 2008 artículo científico 0001-3765 https://www.redalyc.org/articulo.oa?id=32780113 en http://www.redalyc.org/revista.oa?id=327 Anais da Academia Brasileira de Ciências application/pdf Academia Brasileira de Ciências Anais da Academia Brasileira de Ciências (Brasil) Num.1 Vol.80
format Artículo científico
id redalyc_32780113
language en
publishDate 2008
publisher Academia Brasileira de Ciências
spellingShingle Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications
Ohara Augusto
Multidisciplinaria (Ciencias Naturales y Exactas)
tempol
antioxidants
nitric oxide
inflammation
derived oxidants
Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications Ohara Augusto Daniel F. Trindade Edlaine Linares Sandra M. Vaz Multidisciplinaria (Ciencias Naturales y Exactas) tempol antioxidants nitric oxide inflammation derived oxidants The substantial therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) and related cyclicnitroxides as antioxidants has stimulated innumerous studies of their reactions with reactive oxygen species. In comparison,reactions of nitroxides with nitric oxide-derived oxidants have been less frequently investigated. Nevertheless,this is relevant because tempol has also been shown to protect animals from injuries associated with inflammatoryconditions, which are characterized by the increased production of nitric oxide and its derived oxidants. Here, wereview recent studies addressing the mechanisms by which cyclic nitroxides attenuate the toxicity of nitric oxidederivedoxidants. As an example, we present data showing that tempol protects mice from acetaminophen-inducedhepatotoxicity and discuss the possible protection mechanism. In view of the summarized studies, it is proposed thatnitroxides attenuate tissue injury under inflammatory conditions mainly because of their ability to react rapidly withnitrogen dioxide and carbonate radical. In the process the nitroxides are oxidized to the corresponding oxammoniumcation, which, in turn, can be recycled back to the nitroxides by reacting with upstream species, such as peroxynitriteand hydrogen peroxide, or with cellular reductants. An auxiliary protection mechanism may be down-regulation ofinducible nitric oxide synthase expression. The possible therapeutic implications of these mechanisms are addressed. 2008 artículo científico 0001-3765 https://www.redalyc.org/articulo.oa?id=32780113 en http://www.redalyc.org/revista.oa?id=327 Anais da Academia Brasileira de Ciências application/pdf Academia Brasileira de Ciências Anais da Academia Brasileira de Ciências (Brasil) Num.1 Vol.80
title Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications
topic Multidisciplinaria (Ciencias Naturales y Exactas)
tempol
antioxidants
nitric oxide
inflammation
derived oxidants
url https://www.redalyc.org/articulo.oa?id=32780113