Dapsone reduced cuprizone-induced demyelination via targeting Nrf۲ and IKB in C۵۷BL/۶ mice

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 Nrf۲ and IKB. Materials and Methods: MS was induced in C۵۷BL/۶ mice through diet supplementation of CPZ (۰.۲%) for ۶ weeks, and DAP (۱۲.۵ mg/kg/day; IP) was administered for the last ۲ weeks of treatment. Pole test and rotarod performance test, LFB and H&E staining, and Immunohistochemistry (IHC) staining of p-Nrf۲ and p-IKB were performed. Furthermore, superoxide dismutase (SOD) and nitrite were measured.Results: DAP treatment prevented body loss induced by CPZ (P<۰.۰۰۱). Pole test showed that CPZ increased latency time to fall (P<۰.۰۰۰۱) but the latency to reach the floor in the DAP-CPZ group was significantly shorter (P<۰.۰۰۰۱). Rotarod performance test showed the effect of CPZ in reducing fall time in the CPZ group (P<۰.۰۰۱۴); however, DAP significantly increased fall time (P=۰.۰۰۱۲). In LFB staining, DAP reduced demyelination induced by CPZ. CPZ significantly decreased p-Nrf۲ and elevated p-IKB levels compared with the control group (P<۰.۰۰۰۱), but in DAP-treated groups markedly modified these changes (P<۰.۰۰۰۱). 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 Nrf۲ and NF-kB pathways.

کلیدواژه ها:

Cuprizone ، Dapsone ، Multiple sclerosis Neuroinflammation ، NF-kB ، Nrf۲