Evaluation of the prophylactic effect of Amitriptyline and VitD on neuropathy induced by Vincristine

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. VitD, by various mechanisms interferes with the action of reactive oxygen species and nitrogen . Amitriptyline reduse the levels of TNFα and IL_1β through activated lipopolysaccharide in microglial cells effective in neuroprotection. Objective: The aim of the present study was to evaluate the prophylactic effect of simultaneous adiminit ratio of VitD and Amitriptyline 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 Vit D (25, 50, 100, ip, mg / kg) and Amitriptyline (5, 10, 20 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 Amitriptyline and VitD. VitD at doses of 50 mg / kg, 100 mg / kg, ip 100 (P <0.05 and P <0.01) and Amitriptyline at doses of 10 and 20 mg / kg, respectively (P <0.05) decreased vincristine-induced neuropathy. Conclusion: Probably a part of the preventive effects of VitD and Amitriptyline on vincristine-induced neuropathy was produced by inhibiting oxidative stress and improving antioxidant markers.