Effect of Micronized Purified Flavonoid Fraction Containing Hesperidin and Diosmin on Vincristine-Induced Neuropathy in Rats; the Role of Nitric Oxide Pathway.

BACKGROUND

Chemotherapy-induced peripheral neuropathy (CIPN) is a potential complication that can develop following cancer chemotherapy.

OBJECTIVES

Due to limited medical interventions for the prevention and management of CIPN caused by vincristine, a painful and common complication, further research to find the mechanisms of CIPN and the development of effective preventive and therapeutic strategies is needed.

METHODS

We induced CIPN in male Wistar rats by administering intraperitoneal vincristine (VCR) at a dose of 0.1 mg/kg for 10 days. Treatment involved micronized purified flavonoid fraction (MPFF) containing hesperidin and diosmin (MPFF; Daflon®) at doses of 50, 100, and 200 mg/kg. Our investigation focused on levels of inflammatory factors (TNF-α, IL-6) in the dorsal root ganglion (DRG) tissue and included a series of behavioral tests: Von Frey, grip strength, rotarod, open field, and hot plate tests. To examine the role of the nitric oxide (NO) pathway in the effects of MPFF on VCR-induced peripheral neuropathy (VIPN), we also tested the effect of L-arginine (100 mg/kg i.p.) as a NO precursor and L-NAME (20 mg/kg i.p.) as a nitric oxide synthase (NOS) inhibitor.

RESULTS

Based on our behavioral tests, MPFF (50, 100, 200 mg/kg) effectively reduced some symptoms of VIPN, including mechanical allodynia and hyperalgesia. Notably, TNF-α and IL-6 levels in the DRG tissue of the groups treated with 100 and 200 mg/kg of MPFF showed a significant reduction in inflammatory factors. These results underscore the potential of MPFF and the role of the NO signaling pathway in alleviating neuropathic pain caused by VCR.

CONCLUSIONS

Micronized purified flavonoid fraction may be an effective treatment for VIPN by reducing mechanical allodynia, thermal hyperalgesia, and TNF-α and IL-6 levels in DRG tissue. The NO pathway may play a role in the effectiveness of MPFF in treating VIPN.