Most cited article - PubMed ID 28934712
Biotransformation of flubendazole and fenbendazole and their effects in the ribwort plantain (Plantago lanceolata)
In recent years, there has been increasing concern over the environmental risks of the so called "Emerging pollutants (EPs)" that are defined as synthetic or naturally occurring chemicals that are not commonly monitored in the environment but which have the potential to enter the environment and cause adverse ecological and (or) human health effects [...].
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
The nematode Haemonchus contortus, a gastrointestinal parasite of ruminants, can severely burden livestock production. Although anthelmintics are the mainstay in the treatment of haemonchosis, their efficacy diminishes due to drug-resistance development in H. contortus. An increased anthelmintics inactivation via biotransformation belongs to a significant drug-resistance mechanism in H. contortus. UDP-glycosyltransferases (UGTs) participate in the metabolic inactivation of anthelmintics and other xenobiotic substrates through their conjugation with activated sugar, which drives the elimination of the xenobiotics due to enhanced solubility. The UGTs family, in terms of the biotransformation of commonly used anthelmintics, has been well described in adults as a target stage. In contrast, the free-living juvenile stages of H. contortus have attracted less attention. The expression of UGTs considerably varies throughout the life cycle of the juvenile nematodes, suggesting their different roles. Furthermore, the constitutive expression in a susceptible strain with two resistant strains shows several resistance-related changes in UGTs expression, and the exposure of juvenile stages of H. contortus to albendazole (ABZ) and ABZ-sulfoxide (ABZSO; in sublethal concentrations) leads to the increased expression of several UGTs. The anthelmintic drug ABZ and its primary metabolite ABZSO biotransformation, tested in the juvenile stages, shows significant differences between susceptible and resistant strain. Moreover, higher amounts of glycosidated metabolites of ABZ are formed in the resistant strain. Our results show similarly, as in adults, the UGTs and glycosidations significant for resistance-related differences in ABZ biotransformation and warrant further investigation in their individual functions.
- Keywords
- UGT, UHPLC-MS, anthelmintics, biotransformation, drug resistance, gene expression, nematode,
- Publication type
- Journal Article 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