title: Screening of Toxic Effects of Bisphenol A and Products of Its Degradation: Zebrafish (Danio rerio) Embryo Test and Molecular Docking.
abstract: Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, the Medical University of Warsaw , Warsaw, Poland .
authors.forename: Katerina
authors.initials: K
authors.lastname: Makarova
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, the Medical University of Warsaw , Warsaw, Poland .
authors.forename: Pawel
authors.initials: P
authors.lastname: Siudem
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, the Medical University of Warsaw , Warsaw, Poland .
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zawada
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, the Medical University of Warsaw , Warsaw, Poland .
authors.forename: Justyna
authors.initials: J
authors.lastname: Kurkowiak
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D010636:Phenols / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D029941:Fish Proteins; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds