Preventive administration of verapamil attenuates dextran sulfate sodium-induced colitis in mice

Inflammatory bowel disease, including ulcerative colitis (UC) and Crohn's disease, is a chronic immune-mediated disorder characterized by relapsing gastrointestinal inflammation. UC is an idiopathic chronic relapsing-remitting inflammatory disorder affecting the colon, characterized by diarrhea and rectal bleeding. Verapamil, a phenylalkylamine-class L-type calcium channel blocker, has long been used to treat cardiovascular diseases such as hypertension, angina and arrhythmia. The present study aimed to investigate whether verapamil ameliorates UC symptoms in a murine model. In addition, the effects of verapamil on i) inflammatory cytokines, ii) the intestinal microbiota and iii) the intestinal mucosal barrier, all of which are implicated in UC pathogenesis, were investigated. UC was induced in mice by administering 2.5% dextran sulfate sodium (DSS) in the drinking water. Preventive oral administration of verapamil (10 mg/kg/day) initiated 7 days before DSS exposure attenuated body weight loss, diarrhea, and bloody stools in mice with DSS-induced colitis. Verapamil also reduced colonic inflammatory cytokine levels, partially reversed DSS-associated alterations in the intestinal microbiota, and preserved the expression of selected tight junction-related proteins and colonic glutathione levels. These findings suggested that verapamil may exert protective effects in this experimental model of colitis; however, further studies are needed to determine its potential clinical relevance in UC.