The anthelmintic drug ivermectin (IVM), used frequently especially in veterinary medicine, enters the environment mainly via excrements in pastures and could negatively affect non-target organisms including plants. The present study was designed to follow up on our previous investigations into IVM metabolism and its effects in the common meadow plant ribwort plantain (Plantago lanceolata L.) during long-term exposure of both cell suspensions and whole plant regenerants. IVM uptake, distribution, and biotransformation pathways were studied using UHPLC-MS analysis. In addition, the IVM effect on antioxidant enzymes activities, proline concentration, the content of all polyphenols, and the level of the main bioactive secondary metabolites was also tested with the goal of learning more about IVM-induced stress in the plant organism. Our results showed that the ribwort plantain was able to uptake IVM and transform it via demethylation and hydroxylation. Seven and six metabolites respectively were detected in cell suspensions and in the roots of regenerants. However, only the parent drug IVM was detected in the leaves of the regenerants. IVM accumulated in the roots and leaves of plants might negatively affect ecosystems due to its toxicity to herbivorous invertebrates. As IVM exposition increased the activity of catalase, the concentration of proline and polyphenols, as well as decreased the activity of ascorbate peroxidase and the concentration of the bioactive compounds acteoside and aucubin, long-term exposition of the ribwort plantain to IVM caused abiotic stress and might decrease the medicinal value of this herb.

Department of Biochemical Sciences Faculty of Pharmacy in Hradec Králové Charles University Heyrovského 1203 500 05 Hradec Kralove Czech Republic

Laboratory of Plant Biotechnologies Institute of Experimental Botany The Czech Academy of Sciences Rozvojová 313 165 02 Praha 6 Lysolaje Czech Republic

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