Dehpour Ahmad Reza, Khaledi Ehsan, Noori Tayebeh, Mohammadi-Farani Ahmad, Delphi Ladan, Sureda Antoni, Sobarzo-Sanchez Eduardo, Shirooie Samira
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of medical sciences, Tehran, Iran.
Iran J Basic Med Sci. 2022 Jun;25(6):675-682. doi: 10.22038/IJBMS.2022.64993.14310.
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.
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.
DAP treatment prevented body loss induced by CPZ (0.001). Pole test showed that CPZ increased latency time to fall (0.0001) but the latency to reach the floor in the DAP-CPZ group was significantly shorter (0.0001). Rotarod performance test showed the effect of CPZ in reducing fall time in the CPZ group (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 (0.0001), but in DAP-treated groups markedly modified these changes (0.0001). CPZ increased the brain nitrite levels and reduced SOD activity, but in DAP-treated considerably reversed CPZ-induced changes.
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.
多发性硬化症（MS）是一种炎症性疾病，其中中枢神经系统神经细胞的髓鞘会受到损伤。在本研究中，我们评估了氨苯砜（DAP）通过靶向Nrf2和IκB对改善行为功能障碍以及在铜螯合剂（CPZ）诱导的脱髓鞘模型中保护髓鞘的作用。
通过在C57BL/6小鼠的饮食中补充0.2%的CPZ持续6周来诱导MS，在治疗的最后2周给予DAP（12.5mg/kg/天；腹腔注射）。进行爬杆试验和转棒性能测试、LFB和H&E染色以及p-Nrf2和p-IκB的免疫组织化学（IHC）染色。此外，还测量了超氧化物歧化酶（SOD）和亚硝酸盐。
DAP治疗可防止CPZ引起的体重减轻（P=0.001）。爬杆试验表明，CPZ增加了跌落潜伏期（P=0.0001），但DAP-CPZ组到达地面的潜伏期明显缩短（P=0.0001）。转棒性能测试显示CPZ对CPZ组跌落时间有缩短作用（P=0.0014）；然而，DAP显著增加了跌落时间（P=0.0012）。在LFB染色中，DAP减少了CPZ诱导的脱髓鞘。与对照组相比，CPZ显著降低了p-Nrf2水平并升高了p-IκB水平（P=0.0001），但在DAP治疗组中显著改变了这些变化（P=0.0001）。CPZ增加了脑内亚硝酸盐水平并降低了SOD活性，但在DAP治疗组中显著逆转了CPZ诱导的变化。
这些数据支持以下观点，即DAP对CPZ诱导的脱髓鞘的有益作用是通过靶向Nrf2和NF-κB途径介导的。
