Most cited article - PubMed ID 30502705
Metabolism of the anthelmintic drug fenbendazole in Arabidopsis thaliana and its effect on transcriptome and proteome
Although manure is an important source of minerals and organic compounds it represents a certain risk of spreading the veterinary drugs in the farmland and their permeation to human food. We tested the uptake of the anthelmintic drug fenbendazole (FBZ) by soybean, a common crop plant, from the soil and its biotransformation and accumulation in different soybean organs, including beans. Soybeans were cultivated in vitro or grown in a greenhouse in pots. FBZ was extensively metabolized in roots of in vitro seedlings, where sixteen metabolites were identified, and less in leaves, where only two metabolites were found. The soybeans in greenhouse absorbed FBZ by roots and translocated it to the leaves, pods, and beans. In roots, leaves, and pods two metabolites were identified. In beans, FBZ and one metabolite was found. FBZ exposure did not affect the plant fitness or yield, but reduced activities of some antioxidant enzymes and isoflavonoids content in the beans. In conclusion, manure or biosolids containing FBZ and its metabolites represent a significant risk of these pharmaceuticals entering food consumed by humans or animal feed. In addition, the presence of these drugs in plants can affect plant metabolism, including the production of isoflavonoids.
- Keywords
- anthelmintics, antioxidant enzymes, benzimidazoles, biotransformation, isoflavonoids, pharmaceuticals,
- MeSH
- Biological Transport MeSH
- Biotransformation MeSH
- Fenbendazole metabolism pharmacokinetics MeSH
- Glycine max metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Fenbendazole MeSH
Albendazole (ABZ), a widely used anthelmintic drug, enters the environment mainly via livestock excrements. To evaluate the environmental impact of ABZ, the knowledge of its uptake, effects and metabolism in all non-target organisms, including plants, is essential. The present study was designed to identify the metabolic pathway of ABZ and to test potential ABZ phytotoxicity in fodder plant alfalfa, with seeds and in vitro regenerants used for these purposes. Alfalfa was chosen, as it may meet manure from ABZ-treated animals in pastures and fields. Alfalfa is often used as a feed of livestock, which might already be infected with helminths. The obtained results showed that ABZ did not inhibit alfalfa seed germination and germ growth, but evoked stress and a toxic effect in alfalfa regenerants. Alfalfa regenerants were able to uptake ABZ and transform it into 21 metabolites. UHPLC-MS/MS analysis revealed three new ABZ metabolites that have not been described yet. The discovery of the parent compound ABZ together with the anthelmintically active and instable metabolites in alfalfa leaves shows that the contact of fodder plants with ABZ-containing manure might represent not only a danger for herbivorous invertebrates, but also may cause the development of ABZ resistance in helminths.
- Keywords
- UHPLC-MS/MS, anthelmintics, drug metabolism, drug phytotoxicity, drugs in the environment,
- MeSH
- Albendazole pharmacology MeSH
- Anthelmintics pharmacology MeSH
- Germination MeSH
- Animal Feed MeSH
- Medicago sativa drug effects growth & development metabolism MeSH
- Metabolome * MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Albendazole MeSH
- Anthelmintics MeSH
In recent years interest has grown in the occurrence and the effects of pharmaceuticals in the environment. The aim of this work is to evaluate the risk of fertilizing crops with manure from livestock treated with anthelmintics. The present study was designed to follow the fate of the commonly used anthelmintic drug, ivermectin (IVM) and its metabolites in soybeans (Glycine max (L.) Merr.), a plant that is grown and consumed world-wide for its high content of nutritional and health-beneficial substances. In vitro plantlets and soybean plants, cultivated in a greenhouse, were used for this purpose. Our results showed the uptake of IVM and its translocation to the leaves, but not in the pods and the beans. Four IVM metabolites were detected in the roots, and one in the leaves. IVM exposure decreased slightly the number and weight of the beans and induced changes in the activities of antioxidant enzymes. In addition, the presence of IVM affected the proportion of individual isoflavones and reduced the content of isoflavones aglycones, which might decrease the therapeutic value of soybeans. Fertilization of soybean fields with manure from IVM-treated animals appears to be safe for humans, due to the absence of IVM in beans, the food part of plants. On the other hand, it could negatively affect soybean plants and herbivorous invertebrates.
- Keywords
- anthelmintics, antioxidant enzymes, biotransformation, drug metabolites, isoflavonoids,
- MeSH
- Antioxidants metabolism MeSH
- Antiparasitic Agents pharmacology MeSH
- Biological Transport MeSH
- Glycine max drug effects growth & development metabolism MeSH
- Isoflavones metabolism MeSH
- Ivermectin pharmacology MeSH
- Plant Roots drug effects growth & development metabolism MeSH
- Plant Leaves drug effects growth & development metabolism MeSH
- Seeds drug effects growth & development metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antioxidants MeSH
- Antiparasitic Agents MeSH
- Isoflavones MeSH
- Ivermectin MeSH