Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in central nervous system is damaged. Fatigue, lack of coordination, blurred vision and mental problems are some of the symptoms of MS. In the current study, we assessed the performance of Dapsone (DAP) on improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB. MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks and DAP (12.5 mg/kg/day; i.p.) was administered once daily for the last 2 weeks of treatment. Behavioral tests (pole test and rotarod performance test), LFB and H&E staining and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed to evaluate locomotor coordination, observe the area of demyelination in corpus callosum respectively. Furthermore, superoxide dismutase (SOD), and nitrite were measured. Based on the results of the weight of mice, it was shown that the weight of the groups receiving CPZ decreased compared to the control group (P < 0.001), while administration of dapsone increased the weight (P < 0.001). Pole test showed that CPZ increased latency time to fall (P <0.01) but the latency to reach the floor in DAP-CPZ group was significantly shorter than the CPZ group (P <0.001). Rotarod performance test showed the effect of CPZ in reducing fall time in CPZ group (P <0.01) however treatment with DAP significantly increased fall time (P < 0.001). In LFB staining increased demyelination was seen in the CPZ group and decreased demyelination was observed in the DAP group. IHC staining results of p-Nrf2 and p-IKB showed that CPZ significantly decreased p-Nrf2 and elevated p-IKB levels compared with the control group (P <0.001), but in DAP -treated groups markedly modified these changes (P < 0.001). CPZ feeding led to increase of brain nitrite levels and reduced SOD activity (P <0.05) but in DAP-treated considerably reversed CPZ-induced changes in nitrite and SOD activity level (P <0.001). These data support the suggestion that the beneficial properties of dapsone on the CPZ-induced demyelination are mediated by targeting Nrf2 and NF-kB pathways.
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