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<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2024-10-4-0-6</article-id><article-id pub-id-type="publisher-id">3594</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Effect of dalargin on the content of matrix metalloproteinases and tissue inhibitor of metalloproteinases in the colon of mice with experimental ulcerative colitis&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Effect of dalargin on the content of matrix metalloproteinases and tissue inhibitor of metalloproteinases in the colon of mice with experimental ulcerative colitis&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Liashev</surname><given-names>Andrei Yu.</given-names></name><name xml:lang="en"><surname>Liashev</surname><given-names>Andrei Yu.</given-names></name></name-alternatives><email>andr.liashev@yandex.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Mal</surname><given-names>Galina S.</given-names></name><name xml:lang="en"><surname>Mal</surname><given-names>Galina S.</given-names></name></name-alternatives><email>malgs@kursksmu.net</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Artyushkova</surname><given-names>Elena B.</given-names></name><name xml:lang="en"><surname>Artyushkova</surname><given-names>Elena B.</given-names></name></name-alternatives><email>eartyushkova@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Balanina</surname><given-names>Mariya A.</given-names></name><name xml:lang="en"><surname>Balanina</surname><given-names>Mariya A.</given-names></name></name-alternatives><email>balanina99@list.ru</email></contrib></contrib-group><pub-date pub-type="epub"><year>2024</year></pub-date><volume>10</volume><issue>4</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2024/4/НР_БМИ_2024_563-577.pdf" /><abstract xml:lang="ru"><p>Background: Ulcerative colitis is a chronic, multifactorial disease, the development of which is stimulated by disturbances in the microbiota of the colon, poor nutrition, an inadequate immune response to pathogenic and commensal microflora, against a background of genetic predisposition, and has important social implications. Increased levels of matrix metalloproteinases in plasma and colon tissue has been shown in ulcerative colitis. Matrix metalloproteinases-2, 9 and tissue inhibitor of metalloproteinases-2 are important in the development of inflammation in the colon. Existing methods of treating ulcerative colitis are not effective enough. Dalargin has a unique combination of effects, that&amp;rsquo;s why its administration is promising in the treatment of ulcerative colitis. The aim of the study: To investigate dalargin effect on the concentrations of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-2 in the medial colon of mice with experimental ulcerative colitis. Materials and methods: Ulcerative colitis in Balb/C mice was simulated by replacing drinking water with a 5% solution of dextran sodium sulfate in boiled water for 5 days. On the 5th, 7th and 28th days of the experiment, the content of matrix metalloproteinases-2 and 9, tissue inhibitor of metalloproteinases-2, was measured in the homogenate of the medial section of the colon. Dalargin was administered subcutaneously at a dose of 100 mcg/kg for 7 days. Results: An increase in the content of matrix metalloproteinases-2 and 9, as well as tissue inhibitor of metalloproteinases-2, was established in the colon wall of mice with ulcerative colitis on the 5th and 7th days of the experiment. In chronic ulcerative colitis, only tissue inhibitor of metalloproteinases-2 levels were significantly higher than in naive mice. The administration of dalargin caused a decrease in the concentration of matrix metalloproteinases-2 and 9, a tissue inhibitor of metalloproteinases-2, during the acute period of the disease. In chronic ulcerative colitis, administration of dalargin decreased the concentration of tissue inhibitor of metalloproteinases-2 in the wall of the medial section of the colon. Conclusion: Dalargin reduced the content of matrix metalloproteinase-2 and 9 and tissue inhibitor of metalloproteinases-2 in the colon wall of mice with ulcerative colitis on the 5th and 7th days of the experiment. This effect was higher than sulfasalazine one, which is widely used in the ulcerative colitis treatment.</p></abstract><trans-abstract xml:lang="en"><p>Background: Ulcerative colitis is a chronic, multifactorial disease, the development of which is stimulated by disturbances in the microbiota of the colon, poor nutrition, an inadequate immune response to pathogenic and commensal microflora, against a background of genetic predisposition, and has important social implications. Increased levels of matrix metalloproteinases in plasma and colon tissue has been shown in ulcerative colitis. Matrix metalloproteinases-2, 9 and tissue inhibitor of metalloproteinases-2 are important in the development of inflammation in the colon. Existing methods of treating ulcerative colitis are not effective enough. Dalargin has a unique combination of effects, that&amp;rsquo;s why its administration is promising in the treatment of ulcerative colitis. The aim of the study: To investigate dalargin effect on the concentrations of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-2 in the medial colon of mice with experimental ulcerative colitis. Materials and methods: Ulcerative colitis in Balb/C mice was simulated by replacing drinking water with a 5% solution of dextran sodium sulfate in boiled water for 5 days. On the 5th, 7th and 28th days of the experiment, the content of matrix metalloproteinases-2 and 9, tissue inhibitor of metalloproteinases-2, was measured in the homogenate of the medial section of the colon. Dalargin was administered subcutaneously at a dose of 100 mcg/kg for 7 days. Results: An increase in the content of matrix metalloproteinases-2 and 9, as well as tissue inhibitor of metalloproteinases-2, was established in the colon wall of mice with ulcerative colitis on the 5th and 7th days of the experiment. In chronic ulcerative colitis, only tissue inhibitor of metalloproteinases-2 levels were significantly higher than in naive mice. The administration of dalargin caused a decrease in the concentration of matrix metalloproteinases-2 and 9, a tissue inhibitor of metalloproteinases-2, during the acute period of the disease. In chronic ulcerative colitis, administration of dalargin decreased the concentration of tissue inhibitor of metalloproteinases-2 in the wall of the medial section of the colon. Conclusion: Dalargin reduced the content of matrix metalloproteinase-2 and 9 and tissue inhibitor of metalloproteinases-2 in the colon wall of mice with ulcerative colitis on the 5th and 7th days of the experiment. This effect was higher than sulfasalazine one, which is widely used in the ulcerative colitis treatment.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>ulcerative colitis</kwd><kwd>dalargin</kwd><kwd>matrix metalloproteinase-2</kwd><kwd>matrix metalloproteinase-9</kwd><kwd>tissue inhibitor of matrix metalloproteinases-2</kwd></kwd-group><kwd-group xml:lang="en"><kwd>ulcerative colitis</kwd><kwd>dalargin</kwd><kwd>matrix metalloproteinase-2</kwd><kwd>matrix metalloproteinase-9</kwd><kwd>tissue inhibitor of matrix metalloproteinases-2</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Du L, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterology Clinics of North America. 2020;49(4):643-654. DOI: https://doi.org/10.1016/j.gtc.2020.07.005</mixed-citation></ref><ref id="B2"><mixed-citation>Smillie CS, Biton M, Ordovas-Montanes J, et al. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell. 2019;178(3):714-730. DOI: https://doi.org/10.1016/j. cell.2019.06.029</mixed-citation></ref><ref id="B3"><mixed-citation>Shelygin YuA, Ivashkin VT, Belousova EA, et al. Ulcerative colitis (K51), adults. Koloproktologia. 2023;22(1):10-44. Russian. DOI: https://doi.org/10.33878/2073-7556-2023-22-1-10-44</mixed-citation></ref><ref id="B4"><mixed-citation>Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. The Lancet. 2023;402(10401):571-584. DOI: https://doi.org/10.1016/S0140-6736(23)00966-2</mixed-citation></ref><ref id="B5"><mixed-citation>Akinshina AI, Smirnova DV, Zagainova AV, et al. Prospects of Using Microbiota Correction Methods in the Treatment of Inflammatory Bowel Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(2):12-22. Russian. DOI: https://doi.org/10.22416/1382-4376-2019-29-2-12-22</mixed-citation></ref><ref id="B6"><mixed-citation>de Almeida LGN, Thode H, Eslambolchi Y, et al. Matrix Metalloproteases: from molecular mechanisms to Physiology, Pathophysiology, and Pharmacology. Pharmacology Review. 2022;4(3):712-768. DOI: http://doi.org/10.1124/pharmrev.121.000349</mixed-citation></ref><ref id="B7"><mixed-citation>Maronek M, Marafini I, Gardlik R, et al. Metalloproteinases in Inflammatory Bowel Disease. Journal of Inflammation Research. 2021;14:1029-1041. DOI: http://doi.org/10.2147/JIR.S288280</mixed-citation></ref><ref id="B8"><mixed-citation>Efremova OA. Studying the role of interlocus interactions of folate cycle genes and matrix metalloproteinases in the formation of fetal growth retardation. Research Results in Biomedicine. 2022;8(1):36-55. Russian. DOI: http://doi.org/10.18413/2658-6533-2022-8-1-0-3</mixed-citation></ref><ref id="B9"><mixed-citation>Remneva OV, Korenovsky YV, Hovalyg NM, et al. Induced preterm birth: evaluation of oxidative status, matrix metalloproteinases and their tissue inhibitors in amniotic fluid. Research Results in Biomedicine. 2021;7(1):86-95. Russian. DOI: http://doi.org/10.18413/2658-6533-2020-7-1-0-9</mixed-citation></ref><ref id="B10"><mixed-citation>Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. International Journal of Molecular Science. 2020;21(24):9739. DOI: http://doi.org/10.3390/ijms21249739</mixed-citation></ref><ref id="B11"><mixed-citation>Eiro N, Barreiro-Alonso E, Fraile M, et al. Expression of MMP-2, MMP-7, MMP-9, and TIMP-1 by Inflamed Mucosa in the Initial Diagnosis of Ulcerative Colitis as a Response Marker for Conventional Medical Treatment. Pathobiology. 2023;90(2):81-93. DOI: http://doi.org/10.1159/000524978</mixed-citation></ref><ref id="B12"><mixed-citation>Lin X, Li J, Zhao Q, et al. WGCNA Reveals Key Roles of IL8 and MMP-9 in Progression of Involvement Area in Colon of Patients with Ulcerative Colitis. Current Medical Science. 2018;38(2):252-258. DOI: http://doi.org/10.1007/s11596-018-1873-6</mixed-citation></ref><ref id="B13"><mixed-citation>Bulgakov SA. Peptide therapeutics in pancreatology. Russian Journal of Evidence-Based Gastroenterology. 2018;7(4):30-34. Russian. DOI: http://doi.org/10.17116/dokgastro2018704130</mixed-citation></ref><ref id="B14"><mixed-citation>Liashev AYu, Mal GS, Solin AV. Investigation of dalargin effectiveness in experimental ulcerative colitis. Experimental and Clinical Pharmacology. 2023;86(9):7-11. Russian. DOI: http://doi.org/10.30906/0869-2092-2023-86-9-7-11</mixed-citation></ref><ref id="B15"><mixed-citation>Khomyakova TI, Zolotova NA, Khochanskiy DN, et al. The modelling of acute and chronic colitis in mice. Treatment and Prophylaxis. 2013;7 (3):148-159. Russian.</mixed-citation></ref><ref id="B16"><mixed-citation>Lishmanov YuB, Maslov LN, Naryzhnaya NV, et al. Endogenous opioid system as a mediator of acute and long-term adaptation to stress. Prospects for clinical use of opioid peptides. Annals of the Russian Academy of Medical Sciences. 2012;67(6):73-82. Russian.</mixed-citation></ref><ref id="B17"><mixed-citation>Motov VS, Bykova AV, Bykov VV, et al. Protective activity of aminoguanidine derivate on the model of ulcerative colitis in rats. Experimental and Clinical Pharmacology. 2021;84(5):6-10. Russian. DOI: http://doi.org/10.30906/0869-2092-2021-84-5-6-10</mixed-citation></ref><ref id="B18"><mixed-citation>Lipatov VA, Severinov DA, Kryukov AA, et al. Ethical and legal aspects of in vivo experimental biomedical research. Part I. I.P. Pavlov Russian Medical Biological Herald. 2019;27(1):80-92. Russian. DOI: https://doi.org/10.23888/PAVLOVJ201927180-92</mixed-citation></ref><ref id="B19"><mixed-citation>Lipatov VA, Severinov DA, Kryukov AA, et al. Ethical and legal aspects of in vivo experimental biomedical research. Part II. I.P. Pavlov Russian Medical Biological Herald. 2019;27(2):245-257. Russian. DOI: https://doi.org/10.23888/PAVLOVJ2019272245-257</mixed-citation></ref><ref id="B20"><mixed-citation>Derkacz A, Olczyk P, Olczyk K, et al. The role of extracellular matrix components in inflammatory bowel diseases. Journal of Clinical Medicine. 2021;10(5):1122. DOI: https://doi.org/10.3390/jcm10051122</mixed-citation></ref><ref id="B21"><mixed-citation>Luo P, Li X, Gao Y, et al. Central administration of human opiorphin alleviates dextran sodium sulfate-induced colitis in mice through activation of the endogenous opioid system. Frontiers in Pharmacology. 2022;13:904926. DOI: https://doi.org/10.3389/fphar.2022.904926</mixed-citation></ref><ref id="B22"><mixed-citation>Fan L, Qi Y, Qu S, et al. B. adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling. Gut Microbes. 2021;13(1):1-17. DOI: https://doi.org/10.1080/19490976.2020.1826746</mixed-citation></ref><ref id="B23"><mixed-citation>Shamsheya AM, Hussein WM, Elnely DA, et al. Serum matrix metalloproteinase-9 concentration as a marker of disease activity in patients with inflammatory bowel disease. European Journal of Gastroenterology and Hepatology. 2021;31(Suppl.1):e803-e809. DOI: https://doi.org/10.1097/MEG.0000000000002264</mixed-citation></ref><ref id="B24"><mixed-citation>Raeeszadeh-Sarmazdeh M, Do LD, Hritz BG. Metalloproteinases and their inhibitors: potential for the development of new therapeutics. Cell. 2020;9(5):1313. DOI: https://doi.org/10.3390/cell9051313</mixed-citation></ref><ref id="B25"><mixed-citation>Lashgari N-A, Roudsari NM, Zandi N, et al. Current overview of&amp;nbsp;opioids in&amp;nbsp;progression of&amp;nbsp;inflammatory bowel disease; pharmacological and&amp;nbsp;clinical considerations. Molecular Biology Reports. 2021;48(1):855-874. DOI: https://doi.org/10.1007/s11033-020-06095-x</mixed-citation></ref><ref id="B26"><mixed-citation>DiCello JJ, Saito A, Rajasekhar P, et al. Inflammation-associated changes in DOR expression and function in the mouse colon. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2018;315(4):G544-559. DOI: https://doi.org/10.1152/ajpgi.00025.2018</mixed-citation></ref><ref id="B27"><mixed-citation>Bobo TR, Fitzpatrick LR, Whitcomb TC, et al. Role of the &amp;delta;-Opioid Receptor in 2 Murine Models of Colitis. Comparative Medicine. 2020;70(1):25-34. DOI: https://doi.org/1030802/AALAS-CM-19-00002</mixed-citation></ref><ref id="B28"><mixed-citation>Ronsisvalle S, Spadaro A, Tomasello B, et al. Molecular modeling and biological studies show that some &amp;mu;-opioid receptor agonists might elicit analgesia acting as MMP-9 inhibitors. Future Medicinal Chemistry. 2019;11(11):1245-1258. DOI: https://doi.org/10.4155/fmc-2018-0535</mixed-citation></ref><ref id="B29"><mixed-citation>Huang H-M, He X-H, Huang X-Y, et al. Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway. Cell Communication and Signaling. 2022;20(1):35. DOI: https://doi.org/10.1186/s12964-022-00833-3</mixed-citation></ref><ref id="B30"><mixed-citation>&amp;nbsp;</mixed-citation></ref></ref-list></back></article>