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.

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.

The anthelmintics (regularly administered to livestock to control the infections caused by parasitic worms) and their metabolites formed in treated animals are excreted to the environment. This contamination might have a negative influence on non-target organisms including plants. Our previous studies described the uptake, metabolism, and effects of anthelmintics in plants using in vitro models exposed to anthelmintic drugs in solutions. The present study was performed in clover grown in soil fertilized with manure from sheep treated with the recommended dose of albendazole (ABZ), ivermectin (IVM), or monepantel (MOP). The uptake and metabolism of drugs in clover were monitored for six weeks using UHPLC-MS/MS, and several stress markers (proline accumulation, lipid peroxidation, and antioxidant enzymes activities) were evaluated. The results showed that ABZ and MOP were absorbed, metabolized, and translocated to leaves, while IVM was detected only in the roots. No or minimal drug-response was observed in monitored stress markers, and only a temporary increase of several antioxidative enzymes activities was observed. Overall, manure from sheep treated with anthelmintics does not evoke chronic stress in clover, but it can cause the entry of anthelmintics in other organisms and the food-chain.