title: ABCB1 and ABCC4 efflux transporters are involved in methyl parathion detoxification in ZFL cells.
abstract: The multi-xenobiotics resistance (MXR) mechanisms are the first line of defense against toxic substances in aquatic organisms and present great importance in the adaptation related to contaminated environments. Methyl parathion (MP) is a widely used organophosphate pesticide, which has been associated to various toxic effects in organisms. In the present work, we studied the main genes related to efflux transporters in zebrafish liver (ZFL) cells exposed to MP with and without an inhibitor of ABC transporters (verapamil). The results concerning transporters activity showed that the MXR mechanism is activated to detoxify from methyl parathion. The toxic effects of MP on ZFL cells were increased in the presence of the efflux transporter inhibitor, once cell viability was significantly decreased in co-exposure experiments. The combined exposure to MP and the inhibitor caused an increase in gene expression of P-gp1 (Abcb1) and MRP4 (Abcc4), suggesting that these transporters isoforms are associated with MP efflux. In general, the expression of genes related to the antioxidant defense system (ADS) was significantly increased in ZFL cells co-exposed to MP and verapamil. These data provide useful insights for better understanding of MP detoxification mechanism in fish hepatocytes.
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Brazil.
authors.forename: Bruna Félix
authors.initials: BF
authors.lastname: Nornberg
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Brazil.
authors.forename: Carolina Reyes
authors.initials: CR
authors.lastname: Batista
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Brazil.
authors.forename: Daniela Volcan
authors.initials: DV
authors.lastname: Almeida
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Brazil.
authors.forename: Gilma Santos
authors.initials: GS
authors.lastname: Trindade
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Brazil. Electronic address: dqmluf@furg.br.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Marins
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism* / Q000502:physiology; D008743:Methyl Parathion / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism / Q000502:physiology*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018528:ATP-Binding Cassette Transporters; D008743:Methyl Parathion; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029961:Zebrafish Proteins; C000599462:Abcb4 protein, zebrafish; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C000592651:Abcc4 protein, zebrafish
keywords: ABC transporters; Methyl parathion; Multixenobiotic resistance (MXR); Verapamil