Melatonin Decreases Nitric oxide Production, Inducible Nitric oxide Synthase Expression and Lipid Peroxidation Induced by Venezuelan Encephalitis Equine Virus in Neuroblastoma Cell Cultures |
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Authors: | Nereida Valero Luz Marina Espina Jesus Mosquera |
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Affiliation: | (1) Seccion de Virologia, Instituto de Investigaciones Clinicas “Dr. Americo Negrette”. Facultad de Medicina, Universidad del Zulia, Apartado Postal 23, Maracaibo, Estado Zulia, 4001-A, Venezuela;(2) Seccion de Inmunologia y Biología Celular, Instituto de Investigaciones Clinicas “Dr. Americo Negrette”, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela |
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Abstract: | Increased expression of inducible nitric oxide synthase has been shown in murine Venezuelan equine encephalitis (VEE) virus infection. In this experimental model, melatonin (MTL) treatment has shown to be beneficial. The aim of this study was to determine the effect of VEE virus on the nitric oxide (NO) production and lipid peroxidation in neuroblastoma cell cultures, and to investigate the role of MTL during cell-virus interaction. Neuroblastoma cells were co-cultured with VEE virus and treated with MTL at doses ranging from 0 to 1.8 mM, for 6, 12, 24 and 48 h. NO and lipid peroxidation were measured in culture supernatants and in the cellular content by nitrite concentration and thiobarbituric acid assay, respectively. Expression of inducible nitric oxide synthase (iNOS) was determined by indirect immunofluorescence. Increased production of NO and lipid peroxidation products were found in supernatants and cellular contents of VEE virus treated cultures. Both NO and lipid peroxidation were decreased by MTL treatment in a time dependent manner. Increased iNOS expression was observed in VEE virus infected cultures that was reduced by MTL treatment. These results could be related to the beneficial role of MTL in the VEE experimental disease and address the possible therapeutic potential of the hormone in human VEE virus infection. |
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Keywords: | Venezuelan equine encephalitis Virus Togavirus Melatonin Nitric oxide Lipid peroxidation Neuroblastoma cell cultures Thiobarbituric acid Nitrites Virus infection Murine Neurons Protective In vivo Supernatants Cellular content In vitro Antioxidant activity Co-cultures Extracellular Malondialdehyde Nitric oxide synthase Central nervous system Inhibitory effect Viral replication Pathogenesis Brain |
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