Effectiveness of Experimental Colitis Therapy with Original Vitamin D3 Rectal Suppositories

Abstract

Background: Pathogenesis of inflammatory bowel disease (IBD) is insufficiently explored, while most of the therapeutic agents used for IBD cases have undesirable side effects, which restrict their administration.The aim of this research was to study the influence of vitamin D3 formulated into original rectal suppositories on the parameters of clinical score, morphology, and oxidative lipid and protein destruction in the colonic lesion in the cases of experimental colitis (EC). Methods and Results: The experiment was performed on 98 Wistar male rats weighing 210-230 g. EC condition was induced by two-phase administration (dermal application and per rectum) of 3% alcohol solution of oxazolone. Originator polyethylene glycol-based suppositories, which contained 1500 МЕ of vitamin D3, were administered per rectum every 12 hours. Clinical score was defined according to the Disease Activity Index (DAI) scale. Morphometry was run using the software program “ImageScope M” (Russia). Damage of the colonic tissue was estimated on Tissue Damage Index (TDI). The following parameters were determined in the colonic lesion: neutrophil count (NC), lymphocyte count (LC), eosinophil count (EC), histiocyte count (HC), plasma cell count (PC), fibroblast count (FC), the diameter of the ulcerous defect, TDI, MPO expression, and TNF-α expression. The following parameters were determined in the damaged tissue homogenate: lipid peroxidation product count (LPP) and protein oxidative modification (POM) count. In cases of oxazolone-induced EC, on Days 2, 4, and 6, we registered clinical and laboratory signs, an ulcerous defect in the damaged area of the colon, all of which are typical for IBD conditions. There was an increase in DAI (peak on Day 6) and TDI (peak on Day 2). We also found an increase in NC (peak on Day 2), LC (peak on Day 6), EC (peak on Day 2), PC (peak on Day 2), HC (peak on Day 2), and FC (peak on Day 2). There was an increase in MPO expression (peak on Day 2) and TNF-α expression (peak on Days 2 and 4). We observed increases in the primary, secondary, and end LPP counts and the early-phase and late-phase POM counts in spontaneous and induced modes. An administration of 1500ME vitamin D3 rectal suppositories every 12 hours for 6 days decreased the severity of clinical manifestations and DAI. It reduced the area of the ulcerous defect and decreased the TDI on Days 4 and 6 of the experiment. On the background of using vitamin D3 rectal suppositories, we found a decrease in NC, EC, LC, and PC in the damaged area and an increase in HC and FC on Days 2, 4, and 6 from the start of the experiment. Administration of D3 rectal suppositories decreased МРО expression and TNF-α expression on Days 4 and 6 of EC. In the damaged area of the colon, we observed a decrease in the counts of the primary, secondary, and end LPP on Days 4 and 6 of the experiment. We also documented a decrease in the POM count in spontaneous mode on Day 2 and on Day 6 in induced mode. Conclusion: Vitamin D3 as a constituent of originator rectal suppositories in total dose 18,000 МЕ in the pre-clinical phase of EC decreases the intensity of EC clinical manifestations. It reduces the count of the cells that take part in tissue destruction in the colonic wall, of TNF-α and MPO expression levels, and LPP- and POM product count. It increases the count of the cells, which promotes tissue reparation. The obtained results are essential for carrying out further research aimed at elaboration of the mechanism of the D3 effect in cases of IBD and at its possible clinical use.