Fisetin mitigates cisplatin-induced peripheral neuropathy: a behavioral and immunohistochemical study.

Adıgüzel, Cansel; Yildirim, Caner; Çevik, Sena; Yilmaz, Şenay Görücü; Bal, Ramazan

Background: Cisplatin (CIS), a commonly used chemotherapeutic drug, often causes peripheral neuropathy, considerably affecting patients' quality of life. The present study investigated the neuroprotective effects of fisetin, a natural flavonoid with antioxidant and anti-inflammatory features, in a rat model of cisplatin-induced peripheral neuropathy. Methods and results: Male Wistar rats were divided into six groups: sham, neuropathy (CIS, 3 mg/kg, 5 weeks), fisetin treatment (CIS 10 mg/kg and CIS 20 mg/kg), and drugs control groups (10 mg/kg and 20 mg/kg fisetin alone). Behavioural experiments were conducted to evaluate motor coordination and sensory function, electrophysiologically measured nerve conduction velocity (NCV). Gene expression studies were conducted for NF-kB and GPX4 to investigate oxidative stress and inflammation. Finally, confocal microscopy studies were used to evaluate the structure of the sciatic nerve. Cisplatin induced motor impairments, sensory dysfunction, mechanical allodynia, diminished nerve conduction velocity, myelin deterioration (decreased MBP), and increased neuroinflammation (elevated GFAP and NF-kB, decreased GPX4). Fisetin, specifically at a dose of 10 mg/kg, markedly enhanced motor coordination, sensory thresholds, NCV, maintained myelin integrity, reduced glial activation, and restored oxidative and inflammatory balance by elevating GPX4 levels and decreasing NF-kB expression. Conclusions: These results highlight fisetin's potential as a therapeutic agent for cisplatin-induced neuropathy, emphasising its role in restoring molecular, structural, and functional integrity within the peripheral nervous system.

MYELIN basic protein; PERIPHERAL nervous system; MEDICAL sciences; NERVE tissue proteins; LABORATORY rats; CISPLATIN

Molecular Biology Reports, 2025, Vol 52, Issue 1, p1

0301-4851

Academic Journal

10.1007/s11033-025-10465-8