Novel Insights into Pro-Apoptotic and Anti-Proliferative Antilarval Actions of Ivermectin on Camel Nasal Bots (Cephalopina titillator)

Camel nasal myiasis, caused by the larvae of Cephalopina titillator, poses significant health and economic burdens in tropical and subtropical regions. Ivermectin, a widely used antiparasitic, has shown promise, but its detailed tissue damaging effects and its mechanisms on this parasite remain underexplored. This study was aimed to elucidate the mechanism of action of Ivermectin against C. titillator larvae, the causative agent of camel nasal myiasis, by evaluating its histopathological and immunohistochemical effects on larval tissues, focusing on cellular structures, proliferative activity, and apoptosis. Larvae were collected from slaughtered camels in Al-Ahsa, Saudi Arabia, and exposed to Ivermectin (1 μg/ml) for 8 hours. Histopathological analysis assessed tissue damage in the cuticle, muscles, fat bodies, and gut. Immunohistochemistry was performed to detect Proliferating Cell Nuclear Antigen (PCNA) and caspase 3 expressions to evaluate cell proliferation and apoptosis, respectively. Control larvae received vehicle treatment. Ivermectin induced widespread damage across multiple larval strucutres. Structural barriers were compromised through cuticle thinning, locomotion was impaired by extensive muscle degeneration, and metabolic function was disrupted by fat body necrosis and lipid depletion. Digestive capacity was adversely affected by gut epithelial degeneration and brush border disruption. At the cellular level, ivermectin markedly suppressed PCNA expression in gut epithelium, indicating inhibition of tissue renewal, while strongly activating caspase-3-mediated apoptosis in the cuticle, fat body and gut. These combined effects suggest irreversible functional collapse rather than transient paralysis. Ivermectin impairs larval structural and cellular integrity, mobility, and metabolic functions while promoting apoptosis and inhibiting tissue repair. These findings clarify its larvicidal efficacy and support its use in managing C. titillator infestations in camels.