title: Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis.
abstract: Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500 μg/kg bw), MIN (50mg/kg bw) or AA (50mg/kg bw). Infected neuroblastoma cultures (MOI: 1); MLT: 0.5, 1, 5mM, MIN: 0.1, 0.2, 2 μM or AA: 25, 50, 75 μM. Brains were obtained at days 1, 3 and 5. In addition, survival rate of infected treated mice was also analyzed. Viral replication was determined by the plaque formation technique. NO and lipid peroxidation were measured by Griess׳ reaction and thiobarbituric acid assay respectively. Increased viral replication, NO production and lipid peroxidation were observed in both, infected brain and neuroblastoma cell cultures compared with uninfected controls. Those effects were diminished by the studied treatments. In addition, increased survival rate (50%) in treated infected animals compared with untreated infected mice (0%) was found. MLT, MIN and AA have an antiviral effect involving their anti-oxidant properties, and suggesting a potential use of these compounds for human VEE virus infection.
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette". Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela; Sociedad Venezolana de Microbiología, Venezuela. Electronic address: valero.nereida@gmail.com.
authors.forename: Nereida
authors.initials: N
authors.lastname: Valero
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette". Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela. Electronic address: mosquera99ve@yahoo.com.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mosquera
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette". Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela. Electronic address: sirleyalcocer15@gmail.com.
authors.forename: Sirley
authors.initials: S
authors.lastname: Alcocer
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette". Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela. Electronic address: embonilla2008@yahoo.com.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bonilla
authors.affiliation: Instituto de Investigaciones Clínicas "Dr. Américo Negrette". Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela. Electronic address: jennysalazarp@yahoo.com.
authors.forename: Jenny
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Department of Immune System Diseases and Oncology, University Hospital "Príncipe de Asturias", Alcala University, Madrid, Spain. Electronic address: mademons@gmail.com.
authors.forename: Melchor
authors.initials: M
authors.lastname: Álvarez-Mon
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004666:Encephalitis Virus, Venezuelan Equine / Q000378:metabolism; D004685:Encephalomyelitis, Venezuelan Equine / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D015996:Survival Rate; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D008911:Minocycline; D008550:Melatonin; D001205:Ascorbic Acid
keywords: Ascorbic acid; Melatonin; Minocycline; Mouse brain; Oxidative stress; Viral replication