Investigating the Role of 7-Ketocholesterol in Alleviating Inflammatory Bowel Disease (IBD) using an Acute Mouse Model of Chemically Induced IBD 2259324

Abstract Introduction Inflammatory Bowel Disease (IBD) is an inflammatory condition involving complex interactions among the intestinal epithelium, immune system, and gut microbiome. T-helper (Th) cells, particularly CD4+ effector cells, play a significant role in sustained inflammation and tissue damage. This study explores a novel compound, 7-Ketocholesterol (7-KC), an oxysterol, caged in methyl-β-Cyclodextrins (mβCD) for delivery to the cell membrane to disrupt lipid raft-based membrane order. Methods The approach targets CD4+ T cells and inflamed gut tissues in Dextran Sulfate Sodium (DSS)-induced acute IBD mouse model. Disease severity in the 7-KC-treated test and control mice was monitored daily using weight loss, water intake, and stool hemoccult scoring. At the experimental endpoint, mice were euthanized to measure colon length. The proximal, medial, and distal parts of the colon were prepared for histological and immunohistochemical analyses. Results The DSS-only group (disease control) developed severe colitis, confirmed by a significant mean weight loss of 13.92% ± 3.58%, substantial colon shortening (6.97 ± 0.46 cm), and high stool hemoccult scores (2.75±0.46). The 7-KC treatment showed disease mitigation in weight loss, colon length, and stool hemoccult scores. Conclusion These findings show that the treatment with 7-KC alleviated the clinical symptoms in the acute DSS-induced IBD mouse model, suggesting therapeutic benefits of 7-KC. We will present these data along with images of colon histology and assessment of inflammation in the colon. Funding Source Villanova University Topic Categories Translational and Interventional Immunology (TI)