Evaluation of the prophylactic effect of N-acetylcyctein and Duloxetine on neuropathy induced by Vincristine in mice

Abstract

Several mechanisms have been proposed in the emergence of vincristine-induced neuropathy, such as increased synaptic glutamate, glutamate receptor over activity, especially NMDA receptors, increased activity of 5-HT2A receptors and oxidative stress is noted. Glutamate is one of the mediators involved in pain. N-acetylcysteine protects the nerves by various mechanisms by clearing free radicals. Duloxetine is effective in reducing neuropathic pain by inhibiting selective serotonin reuptake and lowering TNF-α and IL-1β levels.

Objective: The aim of the present study was to evaluate the prophylactic effect of simultaneous adiminit ratio of duloxetine and N-acetylcysteine on vincristine-induced neuropathy in male mice.

Materials and methods: 72 male mice weighing 25-35 g were randomly divided into 8 groups. In this study, different doses of doloxetine (60, 30, 15, ip, mg / kg) and nonsterile cysteine (100, 50, 25 ip, mg / kg) were injected to animals three days before administration of vincristine. The effect of different medication regimens on neuropathy was evaluated by Hot-plate test before administration of the drug in the first, second and third weeks. Also lipid peroxidation index (MDA) was measured based on reaction with thiobarbituric acid and total antioxidant activity (TAC) was measured using ELISA. Results: Intraperitoneal injection of vincristine induced neuropathy and increased oxidative stress biomarkers (MDA and TAC). Significant changes in serum levels of TAC and MDA were also observed in different doses of N-acetylcysteine and duloxetine. Duloxetine at doses of 30 mg / kg, 60 mg / kg, ip 60 (P <0.05 and P <0.01) and NAC at doses of 100 and 50 mg / kg, respectively (P <0.05) decreased vincristine-induced neuropathy. Conclusion: Probably a part of the preventive effects of duloxetine and N-acetylcysteine on vincristine-induced neuropathy was produced by inhibiting oxidative stress and improving antioxidant markers.