title: Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster.
abstract: The compounds 4-vinylcyclohexene 1,2-monoepoxide (VCM) and 4-Vinylcyclohexene diepoxide (VCD) are the two downstream metabolites of 4-vinylcyclohexene (VCH), an ovotoxic agent in mammals. In addition, VCM and VCD may be found as by-products of VCH oxidation in the environment. Recently, we reported the involvement of oxidative stress in the toxicity of VCH in Drosophila melanogaster. However, it was not possible to determine the individual contributions of VCM and VCD in VCH toxicity. Hence, we investigated the toxicity of VCM and VCD (10-1000 µM) in flies after 5 days of exposure via the diet. Our results indicated impairments in climbing behaviour and disruptions in antioxidant balance and redox status evidenced by an increase in DCFH oxidation, decreases in total thiol content and glutathione-S-transferase (GST) activity in the flies exposed to VCM and VCD (p<0.05). These effects were accompanied by disruptions in the transcription of the genes encoding the proteins superoxide dismutase (SOD1), kelch-like erythroid-derived cap-n-collar (CNC) homology (ECH)-associated protein 1 (Keap-1), mitogen activated protein kinase 2 (MAPK-2), catalase, Cyp18a1, JAFRAC 1 (thioredoxin peroxidase 1) and thioredoxin reductase 1 (TrxR-1) (p<0.05). VCM and VCD inhibited acetylcholinesterase (AChE) and delta aminolevulinic acid dehydratase (δ-ALA D) activities in the flies (p<0.05). Indeed, here, we demonstrated that different target enzymes and genes were modified by the electrophiles VCM and VCD in the flies. Thus, D. melanogaster has provided further lessons on the toxicity of VCM and VCD which suggest that the reported toxicity of VCH may be mediated by its transformation to VCM and VCD.
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, RS 97105-900, Brazil. Electronic address: amos_abolaji@yahoo.com.
authors.forename: Amos O
authors.initials: AO
authors.lastname: Abolaji
authors.affiliation: Departamento de Bioquimica e Biologia Molecular, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS 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 P
authors.initials: JP
authors.lastname: Kamdem
authors.affiliation: Universidade Federal do Pampa, Caçapava do Sul-Caçapava do Sul, RS, Brazil.
authors.forename: Thiago H
authors.initials: TH
authors.lastname: Lugokenski
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 O
authors.initials: EO
authors.lastname: Farombi
authors.affiliation: 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: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Laboratório de Biologia Molecular-LabDros, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
authors.forename: Élgion L
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, RS 97105-900, Brazil. Electronic address: jbtrocha@yahoo.com.br.
authors.forename: João B T
authors.initials: JBT
authors.lastname: Rocha
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D053138:Cyclohexenes / Q000633:toxicity*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism; D014753:Vinyl Compounds / Q000633:toxicity*
chemical_list: D053138:Cyclohexenes; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527886:Keap1 protein, Drosophila; D000072019:Kelch-Like ECH-Associated Protein 1; D012333:RNA, Messenger; D014753:Vinyl Compounds; C030595:4-vinylcyclohexene monooxide; C012606:4-vinyl-1-cyclohexene dioxide; D002374:Catalase; D013482:Superoxide Dismutase; D054481:Thioredoxin Reductase 1; D019950:Mitogen-Activated Protein Kinase 1; D000110:Acetylcholinesterase; D000623:Porphobilinogen Synthase
keywords: 4-Vinylcyclohexene 1,2-monoepoxide; 4-Vinylcyclohexene diepoxide; Changes in mRNA levels; Disruption of antioxidant homoeostasis; Reactive oxygen and nitrogen species