title: Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster.
abstract: 4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of pesticides, plastic, rubber, flame retardants, and tire production. Although, several studies have reported the ovotoxicity of VCH, information on a possible involvement of oxidative stress in the toxicity of this occupational chemical is scarce. Hence, this study was carried out to investigate further possible mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days old were exposed to different concentrations of VCH (10 µM-1 mM) in the diet for 5 days. Subsequently, the survival and negative geotaxis assays and the quantification of reactive oxygen species (ROS) generation were determined. In addition, we evaluated RT-PCR expressions of selected oxidative stress and antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase). Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid dehydratase (δ-ALA-D), and acetylcholinesterase (AChE) activities were determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and ROS production, as well as inhibitions of GST, δ-ALA-D, and AChE activities (P<0.05). Our results suggest that the VCH mechanism of toxicity is associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant balance, and possible neurotoxic consequences due to decreased AChE activity, and impairments in negative geotaxic behavior. Thus, we conclude that D. melanogaster is a useful model for investigating the toxicity of VCH exposure, and here, we have provided further insights on the mechanism of VCH-induced toxicity.
authors.affiliation: Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria; Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil. Electronic address: amos_abolaji@yahoo.com.
authors.forename: Amos
authors.initials: A
authors.lastname: Olalekan Abolaji
authors.affiliation: Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil; Departamento de Bioquímica, Instituto de Ciências Básica da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS CEP 90035-003, Brazil.
authors.forename: Jean
authors.initials: J
authors.lastname: Paul Kamdem
authors.affiliation: Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil; Universidade Federal do Pampa - UNIPAMPA - Campus Caçapava do Sul - RS - Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Henrique Lugokenski
authors.affiliation: Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil.
authors.forename: Thallita
authors.initials: T
authors.lastname: Kalar Nascimento
authors.affiliation: Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil.
authors.forename: Emily
authors.initials: E
authors.lastname: Pansera Waczuk
authors.affiliation: Drug Metabolism and Molecular Toxicology Research Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Olatunde Farombi
authors.affiliation: Laboratório de Biologia Molecular - LabDros, Universidade Federal de Santa Maria, Santa Maria, Brazil, Rio Grande do Sul 97105-900, Brazil.
authors.forename: Élgion Lúcio
authors.initials: ÉL
authors.lastname: da Silva Loreto
authors.affiliation: Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul 97105-900, Brazil. Electronic address: jbtrocha@yahoo.com.br.
authors.forename: João Batista
authors.initials: JB
authors.lastname: Teixeira Rocha
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D053138:Cyclohexenes / Q000633:toxicity*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000623:Porphobilinogen Synthase / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D053138:Cyclohexenes; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; C013733:4-vinylcyclohexene; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D019950:Mitogen-Activated Protein Kinase 1; D000110:Acetylcholinesterase; D000623:Porphobilinogen Synthase
keywords: 4-Vinylcyclohexene; Antioxidants; Neurotoxicity; Oxidative stress; RT-PCR; mRNA gene expression; δ-ALA-D