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

Abstract

AbstractObjectiveUlcerative colitis (UC) is a relapsing inflammatory health state posing significant worldwide problems. Ezetimibe is a cholesterol-lowering drug having anti-inflammatory and pleiotropic properties.MethodsTwenty-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 findingAA 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-α, IL-6 and NF-κB 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-κB/STAT3/CXCL10 signaling axis. Ezetimibe treatment significantly ameliorated all the aforementioned parameters.ConclusionThis 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-κB/STAT3/CXCL10 signaling axis.