Impact of ivermectin on nerve regeneration following sciatic injury in mice: the consequences of dietary high fructose.

Background/aim: Peripheral nerve injuries (PNIs) are debilitating disorders affecting predominantly the younger generation, often leading to significant disabilities. Current treatment strategies are inadequate for addressing the complex nature of these injuries. Peripheral nerve healing and functional recovery are crucial components of both pathophysiology and therapeutic approaches. High fructose corn syrup (HFCS) is a sweetener frequently used in several beverages and foods. It is associated with several metabolic disturbances including insulin resistance and may impair nerve healing. This study investigated the therapeutic role of ivermectin on nerve regeneration following sciatic nerve injury and evaluated motor and sensorial functions together with histopathological evaluation. Additionally, we aimed to compare nerve healing between animals that consume HFCS and those that do not. Materials and methods: Forty-eight male Swiss albino mice were randomly divided into six groups, with three consuming HFCS-42 (11% v/v) and the other three regular tap water for 8 weeks. On day 28, sciatic nerve injury (SNI) was caused in all groups. Ivermectin (1 mg/kg) or gabapentin (30 mg/kg) treatments were administered to selected groups. Body weight, blood glucose, motor function (rotarod, open field test), and thermal-mechanical sensorial functions were assessed weekly. Finally, insulin levels were measured and histopathological samples were taken. Results: Eight weeks of HFCS consumption impaired mechanical and thermal sensory functions and resulted in histopathologically poor nerve repair. Ivermectin resulted in improved sensorial and faster motor function recovery in the HFCS groups. Elevated plasma insulin levels/HOMA-IR values were diminished by ivermectin in the HFCS groups. In the ivermectin non-HFCS group, histopathology revealed accelerated healing and higher scores in total. Ivermectin also ameliorated mechanical sensation loss after SNI along with cold sensation. Conclusion: Ivermectin accelerated sensorial and motor nerve recovery, resulting in faster nerve healing alongside improved insulin resistance, suggesting it might serve as a potential foundation for developing a new treatment for nerve regeneration after injury.