The severity of the acute phase response in experimental ulcerative colitis under conditions of the use of vitamin D3 in the original rectal suppositories
Abstract
<p align="justify"><strong>Aim</strong><strong>.</strong> To study the effect of vitamin D3 in rectal suppositories on severity of the acute phase response (APR) in experimental ulcerative colitis (UC). <strong>Methods.</strong> Experiments were performed on 49 mature male Wistar rats. UC was induced by cutaneous followed by rectal applications of a 3% oxazolone alcohol solution. Novel polyethylene glycol suppositories (300 mg) containing 1500 IU of vitamin D3 were injected <em>per rectum</em> every 12 hrs for 6 days. Data were collected on days 2, 4, and 6 of UC. The clinical picture was assessed according to the Disease Activity Index (DAI) scale adapted for rats, taking into account body weight, consistency of, and the presence of blood in the feces. The number of blood leukocytes and neutrophils was determined on a hematological analyzer and in blood smears. The functional activity of neutrophils isolated from the blood was evaluated by the absorption of monodisperse latex particles and with the spontaneous and induced NBT test. Serum concentrations of C-reactive protein (CRP), IL-6 and IL-8 were measured by enzyme immunoassay. TNF-α expression in the colon wall was measured by an immunohistochemical method. <strong>Results. </strong>The following changes in APR variables along with a progressive increase in DAI were recorded on days 2, 4, and 6. Expression of colon TNF-α increased, with maximal values on days 4 and 6. Serum IL-6 increased and reached a maximal value on day 4; and serum IL-8 increased, with a maximum on day 6. Serum CRP increased, with a maximum on day 6. The total number of blood leukocytes and the number of stab and segmented neutrophils increased, with maximal values on days 2 and 4. The absorption and NBT-reducing ability of blood neutrophils increased, with maximal values on days 4 and 6. The use of rectal suppositories with vitamin D3 in experimental UC resulted in decreases in DAI, colon TNF-α expression, and the number of blood neutrophils on days 4 and 6; decreases in serum concentrations of IL-6 and CRP, and the absorption and NBT-reducing ability of blood neutrophils on days 2, 4, and 6; and decreases in the serum concentration of IL-8 and in the total number of blood leukocytes on day 6. Severity of clinical manifestations was alleviated with decreases in the expression of colon TNF-α, the serum concentration of IL-6, the number of blood leukocytes and neutrophils, and the NBT-reducing ability of neutrophils decreases. <strong>Conclusion. </strong>Application of the original rectal suppositories with vitamin D3 every 12 hours in experimental UC leads to a decrease in the disease activity index. The severity of clinical manifestations weakens as TNF-α expression, serum IL-6 concentration, number of leukocytes and neutrophils in blood, and decrease of neutrophil NST-reducing capacity decrease.</p>
Downloads
References
2. Takač B., Mihaljević S., Glavaš-Obrovac L., Kibel A., Suver-Stević M., Canecki-Varžić S. et al. Interactions among interleukin-6, c-reactive protein and interleukin-6 (-174) g/c polymorphism in the pathogenesis of crohn's disease and ulcerative colitis. Acta Clin Croat. 2020; 59(1):67-80. doi: 10.20471/acc.2020.59.01.09. https://pubmed.ncbi.nlm.nih.gov/32724277/
3. Zhao J., Wang Y., Gu Q., Du Z., Chen W. The association between serum vitamin D and inflammatory bowel disease. Medicine (Baltimore). 2019; 98(18):e15233. doi: 10.1097/MD.0000000000015233. https://pubmed.ncbi.nlm.nih.gov/31045762/
4. Iyer S.S., Gensollen T., Gandhi A., Oh S.F., Neves J.F., Collin F. et al. Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses. Cell. 2018; 173(5):1123-1134.e11. doi:10.1016/j.cell.2018.04.037. https://pubmed.ncbi.nlm.nih.gov/29775592/
5. Sayar S., Kurbuz K., Kahraman R., Caliskan Z., Atalay R., Ozturk O. et al. A practical marker to determining acute severe ulcerative colitis: CRP/albumin ratio. North Clin Istanb. 2019; 7(1):49-55. doi: 10.14744/nci.2018.78800. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103752/
6. Kaur A., Goggolidou P. Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies. J Inflamm (Lond). 2020; 17:15. doi: 10.1186/s12950-020-00246-4. https://pubmed.ncbi.nlm.nih.gov/32336953/
7. Wang Q., Mi S., Yu Z., Li Q., Lei J. Opening a Window on Attention: Adjuvant Therapies for Inflammatory Bowel Disease. Can J Gastroenterol Hepatol. 2020; 2020:7397523. doi:10.1155/2020/7397523. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441453/
8. Murdaca G., Tonacci A., Negrini S., Greco M., Borro M., Puppo F. et al. Emerging role of vitamin D in autoimmune diseases: An update on evidence and therapeutic implications. Autoimmunity Rev. 2019; 18(9):102350. doi.org/10.1016/j.autrev.2019.102350. https://pubmed.ncbi.nlm.nih.gov/31323357.
9. Wang Y., Zhu J., DeLuca H.F. Where is the vitamin D receptor? Arch Biochem Biophys. 2012; 523:123–133. doi: 10.1016/j.abb.2012.04.001. https://pubmed.ncbi.nlm.nih.gov/22503810/
10. Yang F., Sun M., Sun C. et. al. Associations of C-reactive Protein with 25-hydroxyvitamin D in 24 Specific Diseases: A Cross-sectional Study from NHANES. Sci Rep. 2020; 10(1):5883. doi:10.1038/s41598-020-62754-w. https://pubmed.ncbi.nlm.nih.gov/32246038/
11. Zhao H., Zhang H., Wu H., Li H., Liu L., Guo J. et al. Protective role of 1,25(OH)2 vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice. BMC gastroenterology. 2012; 12:57. doi:10.1186/1471-230X-12-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464614/
12. RF patent No. 2019115328, 2019.05.20. Simonyan E.V., Osikov M.V., Boyko M.S., Bakeeva A.E. Means with vitamin D3 for the treatment of ulcerative colitis in the form of rectal suppositories. RF Patent No. 2709209.2019.Bul. No. 35 (In Russ)
13. Osikov M.V., Simonyan E.V., Bojko M.S., Ogneva O.I., Il'inyh M.A., Vorgova L.V., Bogomolova A.M. The effect of vitamin D3 in the composition of original rectal suppositories on the indicators of oxidative modification of proteins in the large intestine in experimental ulcerative colitis. Bulletin of Experimental Biology and Medicine. 2020; 170(11): 563–568. Doi:10.47056/0365-9615-2020-170-11-563-568 (In Russ)
14. Osikov M.V., Simonyan E.A., Boyko M.S. The effect of vitamin D3 in the composition of rectal suppositories of the original composition on the indices of free radical oxidation in the colon mucosa in the dynamics of experimental ulcerative colitis. Bulletin of the Ural Medical Academic Science. 2020; 17(1):42-52. Doi:10.22138/2500-0918-2020-17-1-42-52 (In Russ)
15. Directive 2010/63 / EU of the European Parliament and of the Council of the European Union of 22 September 2010 on the protection of animals used for scientific purposes. Saint Petersburg 2012 (In Russ)
16. Heller F., Fuss I.J., Nieuwenhuis E.E., Blumberg R.S., Strober W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity. 2002; 17(5):629–638. doi: 10.1016/s1074-7613(02)00453-3. https://pubmed.ncbi.nlm.nih.gov/12433369/
17. Wang X.W., Yang J.H., Cao Q., Tang J.M. Therapeutic efficacy and mechanism of water-soluble extracts of Banxiaxiexin decoction on BALB/c mice with oxazolone-induced colitis. Exp. Ther. Med. 2014; 8(4):1201–1204. doi: 10.3892/etm.2014.1890. https://pubmed.ncbi.nlm.nih.gov/25187824/
18. Freydlin. I.S. Methods of studying phagocytic cells in assessing the immune status of a person: tutorial. Leningrad, 1986. 37 р (In Russ)
19. Osikov M.V., Davydova E.V., Boyko M.S., Bakeeva A.E., Kaigorodtseva N.V., Galeeva I.R. and other. Features of free radical oxidation in the large intestine in ulcerative colitis and Crohn's disease. Bulletin of the Russian State Medical University. 2020; 3: 63-70. DOI: 10.24075 / vrgmu.2020.027 (In Russ)
20. Wang H. Q., Zhang W. H., Wang Y. Q., Geng X. P., Wang M. W., Fan Y. Y. et al. Colonic vitamin D receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis. World journal of gastroenterology. 2020; 26(46):7352–7366. doi:10.3748/wjg.v26.i46.7352. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739157/
21. Naderpoor N., Mousa A., Arango LF.G., Barrett H.L., Dekker N.M., de Courten B. Effect of Vitamin D Supplementation on Faecal Microbiota: A Randomised Clinical Trial. Nutrients. 2019; 11(12):2888. doi:10.3390/nu11122888. https://pubmed.ncbi.nlm.nih.gov/31783602.
22. Olson K.C., Kulling Larkin P.M., Signorelli R., Hamele C.E., Olson T.L., Conaway M.R. et al. Vitamin D pathway activation selectively deactivates signal transducer and activator of transcription (STAT) proteins and inflammatory cytokine production in natural killer leukemic large granular lymphocytes. Cytokine. 2018; 111:551–562. doi: 10.1016/j.cyto.2018.09.016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289695/
23. Jeon S.M., Shin E.A. Exploring vitamin D metabolism and function in cancer. Exp Mol Med. 2018; 50(4):20. doi:10.1038/s12276-018-0038-9. https://pubmed.ncbi.nlm.nih.gov/29657326/
