Fenbendazole, a broad spectrum anthelmintic used especially in veterinary medicine, may impact non-target organisms in the environment. Nevertheless, information about the effects of fenbendazole in plants is limited. We investigated the biotransformation of fenbendazole and the effect of fenbendazole and its metabolites on gene expression in the model plant Arabidopsis thaliana. High-sensitive UHPLC coupled with tandem mass spectrometry, RNA-microarray analysis together with qPCR verification and nanoLC-MS proteome analysis were used in this study. Twelve fenbendazole metabolites were identified in the roots and leaves of A. thaliana plants. Hydroxylation, S-oxidation and glycosylation represent the main fenbendazole biotransformation pathways. Exposure of A. thaliana plants to 5 μM fenbendazole for 24 and 72 h significantly affected gene and protein expression. The changes in transcriptome were more pronounced in the leaves than in roots, protein expression was more greatly affected in the roots at a shorter period of exposure (24 h) and in leaf rosettes over a longer period (72 h). Up-regulated (>2-fold change, p < 0.1) proteins are involved in various biological processes (electron transport, energy generating pathways, signal transduction, transport), and in response to stresses (e.g. catalase, superoxide dismutase, cytochromes P450, UDP-glycosyltransferases). Some of the proteins which were up-regulated after fenbendazole-exposure probably participate in fenbendazole biotransformation (e.g. cytochromes P450, UDP-glucosyltransferases). Finally, fenbendazole in plants significantly affects many physiological and metabolic processes and thus the contamination of ecosystems by manure containing this anthelmintic should be restricted.

• MeSH
• anthelmintika metabolismus   MeSH
• Arabidopsis účinky léků   metabolismus   MeSH
• fenbendazol metabolismus   farmakokinetika   MeSH
• kořeny rostlin metabolismus   MeSH
• listy rostlin metabolismus   MeSH
• proteiny huseníčku účinky léků   metabolismus   MeSH
• proteom účinky léků   metabolismus   MeSH
• proteomika metody   MeSH
• regulace genové exprese u rostlin MeSH
• transkriptom účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH

Although veterinary anthelmintics represent an important source of environmental pollution, the fate of anthelmintics and their effects in plants has not yet been studied sufficiently. The aim of our work was to identify metabolic pathways of the two benzimidazole anthelmintics fenbendazole (FBZ) and flubendazole (FLU) in the ribwort plantain (Plantago lanceolata L.). Plants cultivated as in vitro regenerants were used for this purpose. The effects of anthelmintics and their biotransformation products on plant oxidative stress parameters were also studied. The obtained results showed that the enzymatic system of the ribwort plantain was able to uptake FLU and FBZ, translocate them in leaves and transform them into several metabolites, particularly glycosides. Overall, 12 FLU and 22 FBZ metabolites were identified in the root, leaf base and leaf top of the plant. Concerning the effects of FLU and FBZ, both anthelmintics in the ribwort plantain cells caused significant increase of proline concentration (up to twice), a well-known stress marker, and significant decrease of superoxide dismutase activity (by 50%). In addition, the activities of four other antioxidant enzymes were significantly changed after either FLU or FBZ exposition. This could indicate a certain risk of oxidative damage in plants influenced by anthelmintics, particularly when they are under other stress conditions.

• MeSH
• anthelmintika metabolismus   toxicita   MeSH
• biotransformace MeSH
• fenbendazol metabolismus   toxicita   MeSH
• mebendazol analogy a deriváty   metabolismus   toxicita   MeSH
• metabolické sítě a dráhy účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• Plantago účinky léků   enzymologie   růst a vývoj   MeSH
• veterinární léky metabolismus   toxicita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Albendazole (ABZ) is a benzimidazole anthelmintic widely used especially in veterinary medicine. Along with other drugs, anthelmintics have become one of a new class of micro-pollutants that disturb the environment but the information about their fate in plants remains limited. The present study was designed to test the uptake and biotransformation of ABZ in the ribwort plantain (Plantago lancelota), a common meadow plant, which can come into contact with this anthelmintic through the excrements of treated animals in pastures. Two model systems were used and compared: cell suspensions and whole plant regenerants. In addition, time-dependent changes in occurrence of ABZ and its metabolites in roots, basal parts of the leaves and tops of the leaves were followed up. Ultrahigh-performance liquid chromatography coupled with high mass accuracy tandem mass spectrometry (UHPLC-MS/MS) led to the identification of 18 metabolites of ABZ formed in the ribwort. In both model systems, the same types of ABZ biotransformation reactions were found, but the spectrum and abundance of the ABZ metabolites detected in cell suspensions and regenerants differed significantly. Cell suspensions seem to be suitable only for qualitative estimations of drug biotransformation reactions while regenerants were shown to represent an adequate model for the qualitative as well as quantitative evaluation of drug uptake and metabolism in plants.

• MeSH
• albendazol analýza   metabolismus   MeSH
• anthelmintika analýza   metabolismus   MeSH
• biodegradace MeSH
• biotransformace MeSH
• chromatografie kapalinová MeSH
• látky znečišťující půdu analýza   metabolismus   MeSH
• Plantago růst a vývoj   metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH