Evaluation of the therapeutic effects of mycophenolate mofetil targeting Nrf-2 and NLRP3 inflammasome in acetic acid induced ulcerative colitis in rats

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that increases the risk of colorectal cancer. UC is highly associated with the disturbance of the immune system leading to oxidative stress and chronic inflammation of intestine. Therefore, the current study was conducted to investigate the potential anti-oxidant and antiinflammatory effects of MMF against acetic acid-induced UC that might be associated with the regulation of Nrf-2 and NLRP3 inflammasome signaling. UC was induced in Sprague-Dawley rats by intracolonic instillation of acetic acid. Forty-eight hours post UC induction, MMF (50 mg/kg/day, orally) was given for 8 consecutive days. Then, colon tissues and blood samples were collected. Results showed that MMF significantly attenuated the acetic acid-induced functional, biochemical, and inflammatory injuries in colon. MMF significantly decreased oxidative stress as indicated by the decreased malondialdehyde concentration and the increased total antioxidant capacity, glutathione, catalase, and superoxide dismutase concentrations in colon tissues. MMF also significantly increased Nrf-2 and decreased NLRP3 inflammasome expressions. Moreover, MMF decreased expression of interferongamma and increased expression of interferon-alpha. MMF also significantly decreased expression of proinflammatory cytokines, interleukin IL-1 beta and IL-18. These results suggest that MMF has antioxidant and anti-inflammatory effects against acetic acid-induced UC through the upregulation of Nrf-2, and INF-alpha expression in addition to the suppression of NLRP3 inflammasome and subsequent release of IL1 beta, IL-18 and INF-gamma.

Automated summary

The study demonstrated that MMF has significant antioxidant and anti-inflammatory effects against acetic acid-induced ulcerative colitis. This may be achieved by regulating the Nrf-2 and NLRP3 inflammasome signaling pathways.