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

Abstract

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.