NF-ΚB AND NRF2 PATHWAYS CONTRIBUTE IN THE DEVELOPMENT OF ACUTE AND CHRONIC ULCERATIVE COLITIS INDUCED IN MICE BY DEXTRAN SULPHATE SODIUM | ||||
| Al-Azhar Journal of Pharmaceutical Sciences | ||||
| Article 6, Volume 61, Issue 1, March 2020, Page 77-91 PDF (1021.09 K) | ||||
| Document Type: Review Article | ||||
| DOI: 10.21608/ajps.2020.86017 | ||||
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| Author | ||||
| Abdullatif Ahmed | ||||
| Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt. | ||||
| Abstract | ||||
| Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and it is characterized by high recurrence and relapsing risk. UC affects millions of people worldwide but its pathophysiology remains unclear. In this study, the UC models of BABL/c mice were induced by dextran sulfate sodium (DSS) [3.5% (w/v) for 7 days (acute UC) or 1.5% (w/v) for 2 weeks (chronic UC)]. Herein, we aimed to determine the expression levels of nuclear factor κB (NF-κB ), interleukin-1β (IL-1β), nuclear factor erythroid 2–related factor 2 (Nrf2), Superoxide dismutase (SOD) and nitric oxide (NO) production during acute and chronic DSS-induced colitis in mice and to assess their possible role in the pathogenesis of the disease. Our results showed an increased level of NF-κB, IL-1β and NO in ulcerative colitis group while the levels of both Nrf2 and SOD were markedly decreased. Also, we found a significantly increased levels of NF-κB during the acute and chronic experimental colitis, (P > 0.05 and P >0.01 respectively) compared to control. Moreover, the level of pro-inflammatory cytokine IL-1β was increased in response to the elevated level of NF-𝜅B in both the acute and chronic UC (P > 0.01). Interestingly, we found a significant variation in the expression levels of IL-1β between the acute and chronic DSS-induced colitis (P > 0.01) that seems to be essential for the development of the UC from the acute to the chronic phase. These findings suggested that changing in NF-κB and Nrf2 pathways may be contributed in the development of both the acute and chronic DSS-induced UC in mice. Also, both of NF-κB and IL-1β enhance the development of UC and the progression of the acute intestinal inflammation into the chronic phase. Additionally, IL-1β could be used as diagnostic biomarkers to differentiate between the acute and chronic UC. | ||||
| Keywords | ||||
| Dextran sodium sulfate; Ulcerative colitis; NF-κB; Nrf2; IL-1β; NO; SOD | ||||
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