Ivermectin induces oxidative stress and mitochondrial damage in Haemonchus contortus

Haemonchus contortus poses a severe threat to livestock, leading to substantial economic losses. The extensive use of ivermectin (IVM), an effective anthelmintic drug, has resulted in the development of resistant strains, reducing the drug's effectiveness and making disease management more challenging. Hence, understanding the underlying mechanisms of IVM resistance is crucial. IVM has been shown to induce apoptosis and oxidative stress imbalance in cancer cells, thereby inhibiting tumor growth; however, whether there is a similar impact on H. contortus has not been well-documented. In this study, the biological functions of previously identified resistance-associated genes were investigated, revealing their involvement in apoptosis and oxidative stress. Experiments were conducted to compare cell apoptosis, mitochondrial function, and oxidative stress markers in IVM-treated and untreated sensitive and resistant strains isolated from the field. The findings demonstrated that mitochondrial dysfunction and increased apoptosis were induced by IVM treatment in sensitive strains, as indicated by elevated mitochondrial membrane potential and apoptosis rates. Conversely, stable mitochondrial function and apoptosis levels under IVM exposure were observed in resistant strains. These results provide novel insights into the resistance mechanisms of H. contortus and offer a theoretical basis for future research on overcoming IVM resistance.