IDDF2024-ABS-0277 Effect of ethyl gallate and propyl gallate on dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice: preventive and protective

<h3>Background</h3> Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the digestive system marked by oxidative stress, leukocyte infiltration, and elevation of inflammatory mediators. In this study, we demonstrate the protective effect of ethyl gallate (EG) and propyl gallate (PG), an antioxidant, given through normal drinking water (DW) and copper water (CW) in various combinations, which had a positive effect on the amelioration of DSS-induced ulcerative colitis in C57BL/6J mice. (IDDF2024-ABS-0277-Figure 1. Graphical abstract) <h3>Methods</h3> We successfully determined the levels of proinflammatory cytokines and antioxidant enzymes by ELISA and tracked oxidative/nitrosative stress (RO/NS) by in vivo imaging (IVIS) using L-012 chemiluminescent probe, disease activity index (DAI), histopathological and morphometric analysis of the colon. (IDDF2024-ABS-0277 Figure 2. Schematic representation of the experimental design). <h3>Results</h3> The results revealed that oral administration of EG and PG at a dose of 50 mg/kg considerably reduced the severity of colitis and improved both macroscopic and microscopic clinical symptoms. The level of proinflammatory cytokines (TNF-α, IL-6, IL-1β, and IFN-γ) in colonic tissue was considerably reduced (IDDF2024-ABS-0277 Figure 3. Effect of ethyl gallate propyl gallate and their combination on proinflammatory cytokinin’s such as (a) IL-6, (b) IL-1β, (c) IFN-γ, and (d) TNF-α in DSS-induced colonic tissue at day 21 post-treatment, cytokinin synthesis was quantified by EISA kits). IVIS imaging of animals from the DSS+EG and DSS+PG treated groups showed a highly significant decrease in RO/NS species relative to the DSS control group (IDDF2024-ABS-0277 Figure 4. The abdominal region of C57BL/6J mice with colitis exhibits strong signals during in vivo imaging of RONS utilizing L-012 Chemiluminescence). We also observed lower levels of myeloperoxidase (MPO), nitric oxide (NO), and lipid peroxidation (LPO) and restored levels of GST and superoxide dismutase (SOD) in the DSS+EG-DW/CW, DSS+PG-DW, and DSS+EG+PG/DW groups compared to the DSS alone treated group (IDDF2024-ABS-0277 Figure 5. Effect of ethyl gallate and propyl gallate and their combination on nitrosative (a) NO, and lipid peroxidation (b) LPO in DSS-induced colonic tissue at day 21 post-treatment, antioxidants levels were quantified by ELISA kits, IDDF2024-ABS-0277 Figure 6. Effect of ethyl gallate and propyl gallate and their combination on antioxidants (a) GST &amp; (b) SOD in DSS-induced colonic tissue at day 21 post-treatment, antioxidant production was quantified by ELISA kits). Also, we showed that the EG, PG, and EG+PG treatments significantly reduced the DAI score and counteracted body weight loss and colon shortening in mice with DSS-induced colitis compared to the DSS-only-treated group. <h3>Conclusions</h3> Our study highlights the protective effect of EG and PG in various combinations which, in pre-clinical animals, serve as an anti-inflammatory drug against the severe form of colitis, indicating its potential for the treatment of IBD in humans. In addition, PG was investigated for the first time in this study for its anti-colitogenic effect on normal drinking