Tu1636 Immunomodulatory Effect of Enalapril on Peritoneal Macrophage and Chronic Colitis in Interleukin-10-Deficient Mice

Background and aim : Colorectal cancer (CRC) is increased in inflammatory bowel diseases (IBD). Chemopreventive agents could minimize this risk. Estrogens exert prevention against CRC throught Estrogen Receptor β (ERβ) with an inverse relation with the tumor. ER β induction may be a target in CRC prevention. Phytoestrogens are dietary compounds with higher binding affinity for ERβ than Erα. A blend of the dietary phytoestrogens (silymarin and lignan) and non-starch insoluble fibers (Eviendep, CM&D Pharma) has been tested in an experimental mouse model of AOM/DSS induced colitis, to assess the anti-inflammatory and anti-carcinogenetic properties and to verify whether such effect is related to an increased ERβ expression. Material and methods : A known model of dextran sodium sulfate/azoxymethane induced CRC was used to obtain the best simulation of IBD-related CRC pathogenesis. Seventy-six C57BL/6J male mice were divided into three groups: 35 mice fed a Eviendepmodified diet during the whole carcinogenetic process, 35 fed a standard diet (positive control) and 6 mice with no treatment or modified diet (negative control). Monitoring of colitis and tumorigenesis was performed by a specific video-endoscopic system (Coloview Miniendoscopic System) at 21 weeks. Animals were sacrificed at 22 weeks for histogical and ERs immunohistochemical evaluation. Histological score was: 0 (no dysplasia), 1 (low grade dysplasia), 2 (high grade dysplasia) and 3 (carcinoma). Results : Mortality rate was of 40-50%. At sacrifice, treated animals showed a decrease in number/volume of polyps and in histological score (p,0.05 ANOVA-Bonferroni post hoc test). Only 30% of Eviendepsupplemented mice showed at least 1 CRC compared with the 100% of the positive controls. ERα expression was higher in neoplastic tissue than in normal mucosa both in treated and positive control groups, while ERβ labeling index (LI%) showed a higher value in nonneoplastic tissue of the Eviendep-supplemented group (63.8±4.7) than in positive control (46.6±6.4), resulting similar to the ERβ LI value of negative controls (54.9±7.9) (p,0.05 Fisher Exact Test) Conclusions : Our results suggest a chemopreventive effect of Eviendep on colonic carcinogenesis arising from inflamed tissue, and such an effect associates with an increase ERβ content in the tissue.