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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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/321460 |
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| author | Catarina Raposo Ana Karolina de Santana Nunes Rayana Leal de Almeida Luna Shyrlene Meiry da Rocha Araújo Maria Alice da Cruz-Höfling Christina Alves Peixoto |
| author_facet | Catarina Raposo Ana Karolina de Santana Nunes Rayana Leal de Almeida Luna Shyrlene Meiry da Rocha Araújo Maria Alice da Cruz-Höfling Christina Alves Peixoto |
| author_sort | Catarina Raposo |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-cf1844e7187a4ef988d2cfe94f50e841 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-cf1844e7187a4ef988d2cfe94f50e8412025-02-03T01:12:41ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/321460321460Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination ModelCatarina Raposo0Ana Karolina de Santana Nunes1Rayana Leal de Almeida Luna2Shyrlene Meiry da Rocha Araújo3Maria Alice da Cruz-Höfling4Christina Alves Peixoto5Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, 13083-862 Campinas, SP, BrazilDepartamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, 13083-862 Campinas, SP, BrazilDepartamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, 13083-862 Campinas, SP, BrazilLaboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Av. Professor Moraes Rego, s/n, Cidade Universitária, 50670-420 Recife, PE, BrazilDepartamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, 13083-862 Campinas, SP, BrazilLaboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Av. Professor Moraes Rego, s/n, Cidade Universitária, 50670-420 Recife, PE, BrazilWe 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.http://dx.doi.org/10.1155/2013/321460 |
| spellingShingle | Catarina Raposo Ana Karolina de Santana Nunes Rayana Leal de Almeida Luna Shyrlene Meiry da Rocha Araújo Maria Alice da Cruz-Höfling Christina Alves Peixoto Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2013/321460 |
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