title: Metabolic pathways of benzimidazole anthelmintics in harebell (Campanula rotundifolia).
abstract: Benzimidazoles anthelmintics, which enter into environment primarily through excretion in the feces or urine of treated animals, can affect various organisms and disrupt ecosystem balance. The present study was designed to test the phytotoxicity and biotransformation of the three benzimidazole anthelmintics albendazole (ABZ), fenbendazole (FBZ) and flubendazole (FLU) in the harebell (Campanula rotundifolia). This meadow plant commonly grows in pastures and comes into contact with anthelmintics through the excrements of treated animals. Suspensions of harebell cells in culture medium were used as an in vitro model system. ABZ, FLU and FBZ were not found to be toxic for harebell cells, which were able to metabolize ABZ, FLU and FBZ via the formation of a wide scale of metabolites. Ultrahigh-performance liquid chromatography coupled with high mass accuracy tandem mass spectrometry (UHPLC-MS/MS) led to the identification of 24, 18 and 29 metabolites of ABZ, FLU and FBZ, respectively. Several novel metabolites were identified for the first time. Based on the obtained results, the schemes of the metabolic pathways of these anthelmintics were proposed. Most of these metabolites can be considered deactivation products, but a substantial portion of them may readily be decomposed to biologically active substances which could negatively affect ecosystems.
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Stuchlíková
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Jirásko
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Skálová
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Pavlík
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Szotáková
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Holčapek
authors.affiliation: Laboratory of Plant Biotechnologies, Institute of Experimental Botany, Czech Academy of Science, Rozvojová 263, 165 02 Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Vaněk
authors.affiliation: Laboratory of Plant Biotechnologies, Institute of Experimental Botany, Czech Academy of Science, Rozvojová 263, 165 02 Prague, Czech Republic. Electronic address: podlipna@ueb.cas.cz.
authors.forename: Radka
authors.initials: R
authors.lastname: Podlipná
mesh_terms: D015766:Albendazole / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000378:metabolism*; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D029422:Campanulaceae / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D017753:Ecosystem; D005243:Feces / Q000737:chemistry; D005273:Fenbendazole / Q000378:metabolism; D008463:Mebendazole / Q000031:analogs & derivatives / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; D005273:Fenbendazole; D008463:Mebendazole; D015766:Albendazole; C018945:flubendazole
keywords: Albendazole; Biotransformation; Drug metabolism; Flubendazole; Phytoremediation