title: Sildenafil (Viagra) protective effects on neuroinflammation: the role of iNOS/NO system in an inflammatory demyelination model.
abstract: 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-1 β , 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-1 β 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.
authors: Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, 13083-862 Campinas, SP, Brazil. cataraposa@gmail.com
authors: Catarina
authors: C
authors: Raposo
authors: Ana Karolina de Santana
authors: AK
authors: Nunes
authors: Rayana Leal de Almeida
authors: RL
authors: Luna
authors: Shyrlene Meiry da Rocha
authors: SM
authors: Araújo
authors: Maria Alice
authors: MA
authors: da Cruz-Höfling
authors: Christina Alves
authors: CA
authors: Peixoto
mesh_terms: D000818:Animals; D003471:Cuprizone / Q000633:toxicity; D006152:Cyclic GMP / Q000378:metabolism; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009186:Myelin Sheath / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D003471:Cuprizone; D000068677:Sildenafil Citrate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051549:Glutathione S-Transferase pi; D006152:Cyclic GMP
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