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Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by c...

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Autores principales: Raposo, Catarina, Nunes, Ana Karolina de Santana, Luna, Rayana Leal de Almeida, Araújo, Shyrlene Meiry da Rocha, da Cruz-Höfling, Maria Alice, Peixoto, Christina Alves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736464/
https://www.ncbi.nlm.nih.gov/pubmed/23970812
http://dx.doi.org/10.1155/2013/321460
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author Raposo, Catarina
Nunes, Ana Karolina de Santana
Luna, Rayana Leal de Almeida
Araújo, Shyrlene Meiry da Rocha
da Cruz-Höfling, Maria Alice
Peixoto, Christina Alves
author_facet Raposo, Catarina
Nunes, Ana Karolina de Santana
Luna, Rayana Leal de Almeida
Araújo, Shyrlene Meiry da Rocha
da Cruz-Höfling, Maria Alice
Peixoto, Christina Alves
author_sort Raposo, Catarina
collection PubMed
description We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS(−/−) mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS(−/−) mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS(−/−) mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS(−/−) mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS(−/−) mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects.
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spelling pubmed-37364642013-08-22 Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model Raposo, Catarina Nunes, Ana Karolina de Santana Luna, Rayana Leal de Almeida Araújo, Shyrlene Meiry da Rocha da Cruz-Höfling, Maria Alice Peixoto, Christina Alves Mediators Inflamm Research Article We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS(−/−) mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS(−/−) mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS(−/−) mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS(−/−) mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS(−/−) mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects. Hindawi Publishing Corporation 2013 2013-07-22 /pmc/articles/PMC3736464/ /pubmed/23970812 http://dx.doi.org/10.1155/2013/321460 Text en Copyright © 2013 Catarina Raposo et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Raposo, Catarina
Nunes, Ana Karolina de Santana
Luna, Rayana Leal de Almeida
Araújo, Shyrlene Meiry da Rocha
da Cruz-Höfling, Maria Alice
Peixoto, Christina Alves
Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model
title Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model
title_full Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model
title_fullStr Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model
title_full_unstemmed Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model
title_short Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model
title_sort sildenafil (viagra) protective effects on neuroinflammation: the role of inos/no system in an inflammatory demyelination model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736464/
https://www.ncbi.nlm.nih.gov/pubmed/23970812
http://dx.doi.org/10.1155/2013/321460
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