Ezetimibe alleviates acetic acid-induced ulcerative colitis in rats: targeting the Akt/NF-κB/STAT3/CXCL10 signaling axis

Objective. Ulcerative colitis (UC) is a relapsing inflammatory health state posing significant worldwide problems. Ezetimibe is a cholesterol-lowering drug having anti-inflammatory and pleiotropic properties.Methods. Twenty-four rats were classified into four groups (n = 6). Group (I) was considered negative control. Acetic acid (AA) was instilled intrarectally in groups (II-IV). Group (II) was considered UC-control. Groups (III and IV) were orally treated with Ezetimibe (5 and 10 mg/kg/day; 14 days).Key finding. AA installation resulted in severe macroscopic colonic lesions associated with elevations in the relative colon weight, the wet weight/length ratio and oxidative stress markers in the colorectum tissues. UC-control rats showed significantly elevated colorectal tissue CXCL10 and STAT3 gene expression. Akt, phosphorylated Akt, phosphorylated STAT3, TNF-alpha, IL-6 and NF-kappa B were expressively upregulated in the UC-control group. AA installation also resulted in significant histopathological alterations in the colorectum tissues of UC-control rats along with increasing the colorectal tissues' immunohistochemical iNOS expression. Collectively, these data suggest activation of the Akt/NF-kappa B/STAT3/CXCL10 signaling axis. Ezetimibe treatment significantly ameliorated all the aforementioned parameters.Conclusion. This is the first study to elucidate the modulatory actions of Ezetimibe against oxidative stress and inflammation associated with AA-induced UC in rats. Ezetimibe treatment mitigates UC via downregulation of the Akt/NF-kappa B/STAT3/CXCL10 signaling axis.