Effect of Ivermectin on the Expression of P-Glycoprotein in Third-Stage Larvae of Haemonchus contortus Isolated from China

SIMPLE SUMMARY: Haemonchus contortus is well known as the most harmful gastrointestinal nematode in ruminants, causing serious economic losses worldwide. The overuse of chemical insecticides (e.g., ivermectin) has caused gastrointestinal nematode resistance to develop and spread, resulting in failure in controlling gastrointestinal nematode spread. At the start of our study, four varieties of H. contortus were obtained from diverse regions of China. This study investigated the drug resistance of H. contortus isolates to ivermectin. Additionally, the changes in the P-gp gene transcription levels of third-stage larvae under ivermectin stress at different time points were measured. The results indicated that the YCHc-022 strain was sensitive to ivermectin, but the WSHc-001, WSHc-003, and CYHHc-136 strains displayed different degrees of resistance to ivermectin, in comparison with the ivermectin-sensitive H. contortus found in Australia. Results from the third-stage larvae of H. contortus in response to ivermectin stress revealed a relation between the P-gp genes and the drug resistance of H. contortus to ivermectin; however, it was not suitable for use as an international molecular marker. Our findings are beneficial for screening molecular markers of H. contortus resistance to ivermectin and offer a novel perspective for detecting the drug resistance of gastrointestinal nematodes. ABSTRACT: Haemonchus contortus poses a severe hazard to the healthy development of the sheep industry and threatens the welfare of sheep. Ivermectin is the primary anthelmintic used for the prevention and treatment of H. contortus parasitism. However, the widespread and uncontrolled application of ivermectin has resulted in the development and spread of resistant strains of H. contortus. P-glycoprotein (P-gp) plays important roles in the pharmacology and toxicology of ivermectin, and changes in P-gp expression levels can be used to analyze the resistance of H. contortus to ivermectin. This study aimed to analyze the effects of ivermectin on P-gp expression in H. contortus L3 larvae isolated from China and to evaluate whether changes in P-gp expression levels can be used to analyze resistant H. contortus strains. In the absence of drug treatment, the ivermectin-resistant strains isolated in China showed increased expression of P-gp11 (p < 0.01) compared with sensitive strains from elsewhere, whereas the expressions of P-gp2 and P-gp9.1 were downregulated (p < 0.01). When the same strain was compared before and after drug treatment, obvious differences in expression were observed between the different strains. Ivermectin-induced P-gp expression was found to be very complex among the L3 larvae of different strains. In addition, it was confirmed that using P-gp to determine ivermectin resistance in H. contortus strains from different geographic environments can yield different results.