Milagros Montiel1, Ernesto Bonilla2, Nereida Valero3, Jesús Mosquera2, Luz M Espina2, Yasmir Quiroz4, Melchor Álvarez-Mon5. 1. Departamento de Microbiologia, Escuela de Bioanalisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela. 2. Instituto de Investigaciones Clínicas "Dr. Américo Negrette," Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela. 3. Instituto de Investigaciones Clínicas "Dr. Américo Negrette," Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela valero.nereida@gmail.com. 4. Centro de Investigaciones Biomédicas, Instituto Venezolano de Investigaciones Científicas (IVIC), Maracaibo, Venezuela. 5. Departamento de Enfermedades Inmunitarias y Oncología, Hospital "Príncipe de Asturias," Universidad de Alcalá, Madrid, España.
Abstract
BACKGROUND: Pro-inflammatory and oxidative events during brain Venezuelan equine encephalitis virus infection could lead to apoptosis and induce anti-inflammatory responses (increased expression of CD200). The aim of this study was to determine the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis virus. METHODS: Mice were infected with 10 median lethal doses (LD50) of Venezuelan equine encephalitis virus, treated with melatonin (500 µg/kg bw; three days before infection and during all experimental time) and sacrificed on days 1, 3, and 5 postinfection. Brain samples were obtained at those periods of time. In addition, infected neuroblastoma cell cultures (multiplicity of infection [MOI]: 1) were treated with 0, 0.1, 0.5, and 1 mM of melatonin and analyzed at 2, 4, and 6 h. CD200 and apoptosis expressions were analyzed by immunohistochemistry and TUNEL assay, respectively. Nitrites and malondialdehyde were determined by appropriate biochemical methods. RESULTS: Increased brain expression of apoptosis, nitrite, and malondialdehyde productions and CD200 of infected mice were found. Melatonin diminished those expressions. Similarly, high apoptosis expression and nitrite and malondialdehyde productions on infected neuroblastoma cultures were diminished by melatonin. Melatonin increased the survival rate (25%) in Venezuelan equine encephalitis virus-infected animals compared with untreated infected mice (0%). CONCLUSIONS: Neurological damage during brain Venezuelan equine encephalitis virus infection could be mediated by apoptosis and oxidative stress and CD200 molecule could be an important anti-inflammatory response. Melatonin could be beneficial reducing apoptosis and oxidative stress.
BACKGROUND: Pro-inflammatory and oxidative events during brain Venezuelan equine encephalitis virus infection could lead to apoptosis and induce anti-inflammatory responses (increased expression of CD200). The aim of this study was to determine the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis virus. METHODS:Mice were infected with 10 median lethal doses (LD50) of Venezuelan equine encephalitis virus, treated with melatonin (500 µg/kg bw; three days before infection and during all experimental time) and sacrificed on days 1, 3, and 5 postinfection. Brain samples were obtained at those periods of time. In addition, infected neuroblastoma cell cultures (multiplicity of infection [MOI]: 1) were treated with 0, 0.1, 0.5, and 1 mM of melatonin and analyzed at 2, 4, and 6 h. CD200 and apoptosis expressions were analyzed by immunohistochemistry and TUNEL assay, respectively. Nitrites and malondialdehyde were determined by appropriate biochemical methods. RESULTS: Increased brain expression of apoptosis, nitrite, and malondialdehyde productions and CD200 of infected mice were found. Melatonin diminished those expressions. Similarly, high apoptosis expression and nitrite and malondialdehyde productions on infected neuroblastoma cultures were diminished by melatonin. Melatonin increased the survival rate (25%) in Venezuelan equine encephalitis virus-infected animals compared with untreated infected mice (0%). CONCLUSIONS:Neurological damage during brain Venezuelan equine encephalitis virus infection could be mediated by apoptosis and oxidative stress and CD200 molecule could be an important anti-inflammatory response. Melatonin could be beneficial reducing apoptosis and oxidative stress.
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