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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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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. |
format | Online Article Text |
id | pubmed-3736464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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