P-1 Potential neuroprotective effects of losartan and donepezil on oxaliplatin-induced peripheral neuropathy in rats

Oxaliplatin (OXL) is a platinum-based antineoplastic drug widely used for treating colorectal cancer which induces peripheral neuropathy as dose-limiting toxicity. We assess the neuroprotective effects of losartan (LOS) and donepezil (DPZ) on OXL-induced in rats. Forty Sprague-Dawley rats were divided into four groups; control (vehicle-treated), OXL (2.4 mg/kg/d; intraperitoneal), OXL+LOS (100 oral), OXL+DPZ (1 oral). All given 5 times/week 2 weeks. Behavioral assessment pain, sensory, motor disturbances was done days 7 14 using paintbrush, acetone, tail-flick latency, grip strength tests. The levels interleukin (IL)-1β, tumor necrosis factor (TNF)-α measured L4-L6 samples. Histopathological examination sciatic nerve to degeneration. induced significant mechanical dynamic allodynia, cold thermal hyperalgesia compared group. LOS significantly ameliorated while DPZ improved allodynia hyperalgesia. increased IL-1β, TNF-α Only attenuated these markers. In group, axons swollen, fiber degeneration with neuron gaps occurred. Both treatments histopathological changes. attenuate neurotoxic effect oxaliplatin by attenuating behavioral alterations protective may involve inhibition spinal pro inflammatory cytokines. Therefore, are promising agents prevent OXA-induced neuropathy.