Dapsone reduced cuprizone-induced demyelination via targeting Nrf2 and IKB in C57BL/6 mice

Abstract

Objective(s): Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in the central nervous system is damaged. In the current study, we assessed the effect of Dapsone (DAP) on the improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB. Materials and Methods: MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks, and DAP (12.5 mg/kg/day; IP) was administered for the last 2 weeks of treatment. Pole test and rotarod performance test, LFB and H&E staining, and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed. Furthermore, superoxide dismutase (SOD) and nitrite were measured.Results: DAP treatment prevented body loss induced by CPZ (P<0.001). Pole test showed that CPZ increased latency time to fall (P<0.0001) but the latency to reach the floor in the DAP-CPZ group was significantly shorter (P<0.0001). Rotarod performance test showed the effect of CPZ in reducing fall time in the CPZ group (P<0.0014); however, DAP significantly increased fall time (P=0.0012). In LFB staining, DAP reduced demyelination induced by CPZ. CPZ significantly decreased p-Nrf2 and elevated p-IKB levels compared with the control group (P<0.0001), but in DAP-treated groups markedly modified these changes (P<0.0001). CPZ increased the brain nitrite levels and reduced SOD activity, but in DAP-treated considerably reversed CPZ-induced changes. Conclusion: These data support the suggestion that the beneficial properties of DAP on the CPZ-induced demyelination are mediated by targeting Nrf2 and NF-kB pathways.

Keywords

• cuprizone
• dapsone
• multiple sclerosis neuroinflammation
• nf-kb
• nrf2