Neuroprotective and Anti-nociceptive Effects of Roflumilast on Vincristine- Induced Neuropathy in Rats

Abstract

       Chemotherapy drugs such as vincristine (VIN) can induce neuropathy, and there is still absence of perfect plan to treat it. The present study was considered to explore effect of roflumilast (Rof.), which is a selective phosphodiesterase 4 (PDE4) inhibitor on VIN-induced neuropathy in rats model. VIN (100 µg/kg, i.p. for 5 days, stop 2 days, and then continued for 5 days) was administered to induce painful neuropathy model in rats. Rof. (3 mg/kg, oral) and gabapentin (60 mg/kg, oral) were administered before 3 days from inj. of VIN and continued for 3 weeks. Numerous parameters were performed; the behavioral tests measurement at different days (0, 7, 14, and 21); rota rod, thermal hyperalgesia (hot plate), and cold allodynia (tail immersion) tests. Measurement of biochemical parameters; measuring; tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) in serum and Nitric oxide (NO) and malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione(GSH) levels in nerve tissue,  Furthermore, histopathological changes in sciatic nerves were also studied. Administration of Rof significantly improved the VIN-induced behavioral alterations, biochemical parameters and histopathological changes. Co-administered Rof. Ameliorated VIN-induced painful neuropathy, which might be attributed to neuroprotective and antinociceptive effects by subsequent reduction in oxidative stress and anti-inflammatory actions.