title: Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test.
abstract: The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Biomedicine and Veterinary Public Health, Box 7028, SE-75007, Uppsala, Sweden. Anna.Mattsson@slu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Mattsson
authors.forename: Erik
authors.initials: E
authors.lastname: Ullerås
authors.forename: Johan
authors.initials: J
authors.lastname: Patring
authors.forename: Agneta
authors.initials: A
authors.lastname: Oskarsson
mesh_terms: D015766:Albendazole / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics / Q000633:toxicity*; D000072467:Cytochrome P450 Family 2; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000502:physiology; D047108:Embryonic Development / Q000187:drug effects*; D006257:Head / Q000002:abnormalities; D006321:Heart / Q000502:physiology; D006330:Heart Defects, Congenital; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013623:Tail / Q000002:abnormalities; D015027:Zebrafish / Q000002:abnormalities / Q000502:physiology
chemical_list: D000871:Anthelmintics; C089877:Cyp2c6v1 protein, rat; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase; D015766:Albendazole