Prevention of Vincristine-induced Peripheral Neuropathy by Methanolic Extract of Bee Pollen and Pentoxifylline in Mice

Background: Anticancer drug-induced neuropathy is a common side effect that results from multiple mechanisms, such as neuroinflammation and oxidative stress. This study evaluated the potential preventive and therapeutic effects of bee pollen methanolic extract (BPE), known for its anti-inflammatory properties, and pentoxifylline, an antioxidant, on vincristine-induced neuropathy. Methods: A total of 90 male mice weighing 20-25 g were randomly divided into nine groups. Different doses of BPE (100, 200, 400 mg/kg/ip) and pentoxifylline (25, 50, 100 mg/kg/ip) were administered 3 days before vincristine injection and neuropathy induction. On the fourth day, vincristine (0.1 mg/kg/ip) was administered as a single dose. Then, it was administered along with the drugs for 10 days. Subsequently, vincristine was discontinued, and only the drugs were injected. Finally, the hot-plate test was performed in all animals to assess neuropathy on days 4, 8, 12, 14, and 17, and sampling was performed for biochemical evaluations on the 17th day. Results: The findings indicated that BPE and pentoxifylline prevented vincristine-induced neuropathy, with varying effects observed at different doses. Conversely, their low doses and combination proved significantly effective in behavioral tests. The low dose of BPE enhanced total antioxidant capacity (TAC) levels, while the low dose of pentoxifylline reduced malondialdehyde (MDA) levels, improving neuropathy. Conclusion: The combination of pentoxifylline and BPE helps prevent vincristine-induced neuropathy by regulating lipid peroxidation mechanisms and enhancing antioxidant capacity.