The role of taxifolin treatment in a peripheral neuropathy model induced by vincristine in rats: NLRP3-mediated effects

Vincristine is a chemotherapeutic agent frequently used in pediatric oncology, which causes treatment delays and a decrease in patients' quality of life due to its peripheral neuropathy side effect. In our study, we aimed to investigate the effects of taxifolin on the NLRP3 pathway, one of the mechanisms involved in the peripheral neuropathy caused by vincristine. Thirty-two male Wistar albino rats were divided into four groups of eight. Group 1 was the control group, group 2 was the vincristine (VCR) group, group 3 was the vincristine+taxifolin 25 mg/kg (VCR+TAX25) group, and group 4 was the vincristine+taxifolin 50 mg/kg (VCR+TAX50) group. The drugs and substances were administered to these groups at the specified doses and intervals. In our study, mechanical allodynia, thermal hyperalgesia, and cold allodynia were performed as behavioral tests. The activity meter test, rotarod test, and paw print test were performed to evaluate motor function and coordination. Electromyography (EMG) measurements were performed to evaluate motor conduction velocity. Immunohistochemically, CD68, IL-1β, IL-18, NF-kB, NLRP3, and Caspase-1 immunoreactivity were evaluated in the sciatic nerve and dorsal root ganglia. In addition, histopathological evaluations were performed on the sciatic nerve, dorsal root ganglia, liver, and kidney. Behavioral tests, motor coordination tests, and EMG assessments revealed significant changes in the VCR+TAX50 group compared to the VCR group, showing similarity to the control group, while no effect of this magnitude was observed in the model formed in the VCR+TAX25 group. Findings in both groups were supported by immunohistochemical assessments of the sciatic nerve. Based on all the data obtained, it is thought that the high dose of taxifolin we used exhibits analgesic and antiallodynic effects, and that these effects may be related to its NLRP3-mediated anti-inflammatory and neuroprotective effects.