Environment-like exposure of free-living stages of Haemonchus contortus to albendazole: the intra- and intergeneration stability of altered expression of UDP-glycosyl transferases and ABC-transporters

Anthelmintic drugs are widespread environmental contaminants, but the consequences of their presence in the environment are still poorly understood. It is known that contact of parasitic nematode Haemonchus contortus with traces of anthelmintic drug albendazole (ABZ) altered the expression and activity of several UDP-glycosyl transferases (UGTs) and P-glycoproteins (Pgps, belonging to ABC-transporters), key enzymes in endogenous metabolism as well as in the defence against xenobiotics, including anthelmintics. However, it is not known whether the changes in expression patterns will last during the life cycle and pass to the next generations. In the present study simulating the environmental-like exposure, free-living stages of H. contortus were exposed or unexposed to a sub-lethal dose of ABZ and its transformation products during L3 development. The L3 served for lambs´ infection and H. contortus adults obtaining. The excrements from infected lambs were used to cultivate the second generation of L3, which were again exposed or unexposed to ABZ and its transformation products during development. The expression pattern of UGTs and Pgps was analysed and compared in the first generation of L3, in the adults, and in the second generation of L3. The results showed that ABZ exposition during larvae development altered the expression of several ugt and pgp genes in L3 and adults. The intrageneration stability of ABZ-evoked changes was observed in the case of ugt24b1, ugt368a1, and pgp11 expression. Concerning intergeneration stability, four genes (ugt365a1, ugt26a2, ugt368b1, and pgp13) maintained the altered expression in the second generation. Interestingly, ABZ-induced changes in the expression of some genes became apparent only in the second generation of L3. Taking together, contact of free-living stages of H. contortus with traces of ABZ and its metabolites in the environment evokes changes in the expression of certain UGTs and Pgps, with some of these changes being intra- and inter-generation stable.