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. 2022 Jun;25(6):675-682.
doi: 10.22038/IJBMS.2022.64993.14310.

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

Ahmad Reza Dehpour  1   2 , Ehsan Khaledi  3 , Tayebeh Noori  4 , Ahmad Mohammadi-Farani  5   6 , Ladan Delphi  7 , Antoni Sureda  8   9 , Eduardo Sobarzo-Sanchez  10   11 , Samira Shirooie  4
Affiliations

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

Ahmad Reza Dehpour et al. Iran J Basic Med Sci. 2022 Jun.

Abstract

Objectives: 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; NF-kB; Neuroinflammation; Nrf2.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The body weight changes (n=7)
Figure 2
Figure 2
Behavioral tests (n=7)
Figure 3
Figure 3
LFB staining of the corpus callosum (×100)
Figure 4
Figure 4
Photomicrograph of prefrontal cortex hematoxylin and eosin staining (×100). Dystrophy of neurons including chromatolysis and irregular Nissl granule distribution (arrows) and vacuolated neurons (arrowheads) in the CPZ group is shown, but neurons in the control and the DAP+CPZ group are nearly normal. (n=4)
Figure 5
Figure 5
A: Photomicrograph of anti p-Nrf2 immunohistochemistry staining (IHC) of the prefrontal cortex (×100). B: Quantification of the IHC results. (n=4). ****P<0.0001 vs the control group, ####P<0.0001 vs the CPZ group
Figure 6
Figure 6
A: Photomicrograph of anti-p-IKB immunohistochemistry staining (IHC) of the prefrontal cortex (×100). B: Quantification of the IHC results. (n=4). ****P<0.0001 vs the control group, ####P<0.0001 vs the CPZ group
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