Anticolitis effect of febuxostat. The imperative role of NLRP-3/Caspase-1/IL-1β pathway via histopathological, immunohistochemical and biochemical approach.

BACKGROUND

Ulcerative colitis (UC) is a persistent inflammation of the mucous membrane of the large intestine, mostly impacting the colon and rectum. Lack of secure and efficient medical treatments motivates the search for new therapeutic agents to efficiently manage UC and its associated outcomes. The objective of this study was to investigate the preventive effect of febuxostat in rats with UC caused by acetic acid (AA).

METHODS

AA (2 ml, 3% v/v) was administered intrarectally to induce UC. Preceding the administration of AA, febuxostat (10 mg/kg/day) was orally administered for two weeks.

RESULTS

Febuxostat suppressed AA-induced UC by ameliorating colonic histological alterations, including inflammation, glandular hyperplasia, goblet cell loss, and mucosal ulcerations, while simultaneously reducing colon weight, malondialdhyde, and interleukin-18 contents. Febuxostat successfully rectified the metabolic imbalance between oxidants and antioxidants induced by AA. Furthermore, febuxostat decreased the levels of caspase-1 and NOD-LRR and pyrin domain containing protein 3 and increased colon length, catalase activity, and zonula occludens-1 expression.

CONCLUSION

Febuxostat mitigated AA-induced UC in rats by influencing the NLRP3/caspase-1/IL-1β signaling pathway, controlling the equilibrium between oxidants and antioxidants, and improving the integrity of the barrier of the colon.