title: Interference with xenobiotic metabolic activity by the commonly used vehicle solvents dimethylsulfoxide and methanol in zebrafish (Danio rerio) larvae but not Daphnia magna.
abstract: Organic solvents, such as dimethylsulfoxide (DMSO) and methanol are widely used as vehicles to solubilise lipophilic test compounds in toxicity testing. However, the effects of such solvents upon innate detoxification processes in aquatic organisms are poorly understood. This study assessed the effect of solvent exposure upon cytochrome P450 (CYP)-mediated xenobiotic metabolism in Daphnia magna and zebrafish larvae (4d post fertilisation). Adult D. magna were demonstrated to have a low, but detectable, metabolism of ethoxyresorufin in vivo and this activity was not modulated by pre-exposure to DMSO or methanol (24 h, up to 0.1% and 0.05% v/v, respectively). In contrast, the metabolism of ethoxyresorufin in zebrafish larvae was significantly reduced by both solvents (0.1% and 0.05% v/v, respectively) after 24 h of exposure. In zebrafish, these observed decreases in activity towards ethoxyresorufin were accompanied by decreased expression of a variety of genes coding for drug metabolising enzymes (corresponding to CYP1, CYP2, CYP3 and UDP-glucuronyl transferase [UGT] family enzymes), measured by quantitative PCR. Reduction of gene expression and CYP1 enzyme activities by methanol (0.05% v/v) in zebrafish larvae was partially reversed by co-exposure with Aroclor 1254 (100 μg L(-1)). Overall this study suggests that relatively low concentrations of organic solvents can impact upon the biotransformation of certain xenobiotics in zebrafish larvae, and that this warrants consideration when assessing compounds for metabolism and toxicity in this species.
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. r.david@imperial.ac.uk
authors.forename: Rhiannon M
authors.initials: RM
authors.lastname: David
authors.forename: Huw S
authors.initials: HS
authors.lastname: Jones
authors.forename: Grace H
authors.initials: GH
authors.lastname: Panter
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Winter
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutchinson
authors.forename: J
authors.initials: J
authors.lastname: Kevin Chipman
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003621:Daphnia / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000432:Methanol / Q000378:metabolism* / Q000633:toxicity; D010078:Oxazines / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000633:toxicity; D015262:Xenobiotics / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D010078:Oxazines; D014874:Water Pollutants, Chemical; D015262:Xenobiotics; D029961:Zebrafish Proteins; C007649:ethoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase; D000432:Methanol; D004121:Dimethyl Sulfoxide