The possible protective effect of metformin on acute experimental colitis induced by dextran sodium sulfate in mice

Abstract

Introduction Dextran sulfate sodium (DSS)-induced colitis is a widely used model of large intestinal damage that closely resembles human ulcerative colitis. Aim The aim of this study was to evaluate the possible protective effect of metformin on the expression of metallothionein (MT) and nuclear factor κB (NF-κB), apoptosis, and proliferation in a DSS-induced colitis model. Materials and methods Eighteen adult albino mice were divided into three groups and were treated for 7 consecutive days as follows: group I served as the control group; group II (the DSS group) received 3% DSS in drinking water; and group III (the DSS+metformin group) received 3% DSS in drinking water plus metformin at a dose of 200 mg/kg. The severity of the disease was evaluated on the basis of changes in body weight and the disease activity index. At the end of the experiment, the colon length was measured and the distal colon was processed for histological examination and immunohistochemical staining with MT, NF-κB (p65), caspase-3, or proliferating cell nuclear antigen. Results Metformin significantly improved the loss of body weight and the shortening of the colon and significantly decreased the disease activity index and histological scores in DSS-induced colitis. However, these parameters, with the exception of colon length, were still significantly higher compared with control values. Metformin treatment reduced the overexpression of NF-κB and MT in the mucosa and submucosa induced by DSS treatment. It also decreased the number of apoptotic cells and increased the number of proliferating cells. Conclusion Metformin attenuated DSS-induced colonic injury and inflammation in mice through modulation of MT and NF-κB expression and reduction of apoptosis and thus may have a protective effect in inflammatory bowel disease.