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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Bulletin of Rehabilitation Medicine</journal-id><journal-title-group><journal-title>Bulletin of Rehabilitation Medicine</journal-title></journal-title-group><issn publication-format="print">2078-1962</issn><issn publication-format="electronic">2713-2625</issn><publisher><publisher-name>National Medical Research Center for Rehabilitation and Balneology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">632618</article-id><article-id pub-id-type="doi">10.38025/2078-1962-2024-23-2-25-33</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Collagen hydrogel protects intestinal epithelial cells from indomethacin-induced damage: results of an in vitro experiment</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4803-4803</contrib-id><name name-style="western"><surname>Markov</surname><given-names>Pavel A.</given-names></name><email>markovpa@nmicrk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0685-5109</contrib-id><name name-style="western"><surname>Sokolov</surname><given-names>Andrey S.</given-names></name><email>markovpa@nmicrk.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3559-2435</contrib-id><name name-style="western"><surname>Artemyeva</surname><given-names>Irina A.</given-names></name><email>markovpa@nmicrk.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6743-2615</contrib-id><name name-style="western"><surname>Gilmutdinova</surname><given-names>Ilmira R.</given-names></name><email>markovpa@nmicrk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3097-8889</contrib-id><name name-style="western"><surname>Fesyun</surname><given-names>Anatoliy D.</given-names></name><email>markovpa@nmicrk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8832-8470</contrib-id><name name-style="western"><surname>Eremin</surname><given-names>Petr S.</given-names></name><email>markovpa@nmicrk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff id="aff-1">National Medical Research Center for Rehabilitation and Balneology</aff><aff id="aff-2">FIRST ALIVE COLLAGEN Limited Liability Company</aff><pub-date date-type="pub" iso-8601-date="2024-05-24" publication-format="electronic"><day>24</day><month>05</month><year>2024</year></pub-date><volume>23</volume><issue>2</issue><fpage>25</fpage><lpage>33</lpage><history><date date-type="received" iso-8601-date="2024-05-24"><day>24</day><month>05</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-05-24"><day>24</day><month>05</month><year>2024</year></date></history><permissions><copyright-statement>Copyright © 2024, Markov P.A., Sokolov A.S., Artemyeva I.A., Gilmutdinova I.R., Fesyun A.D., Eremin P.S.</copyright-statement><copyright-year>2024</copyright-year></permissions><abstract>&lt;p&gt;&lt;bold&gt;INTRODUCTION.&lt;/bold&gt; Indomethacin is a derivative of indoleacetic acid and has anti-inflammatory, analgesic and antipyretic effects. However, the results of numerous studies show that indomethacin, like many other nonsteroidal anti-inflammatory drugs (NSAIDs), have an inhibitory effect on the viability and functional activity of enterocytes. In this regard, the search for new ways to reduce the severity of side effects from the use of NSAIDs remains relevant. One of these approaches may be to enrich patients’ diets with non-drug biologically active compounds, including proteins. However, the effect of dietary proteins and biologically active peptides on NSAID-induced damage to the wall of the small intestine and stomach has not been sufficiently studied.&lt;/p&gt;&#13;
&lt;p&gt;&lt;bold&gt;AIM.&lt;/bold&gt; To evaluate the ability of a collagen-containing dietary supplement to protect human duodenal epithelial cells (HuTu-80 line) from indomethacin-induced damage.&lt;/p&gt;&#13;
&lt;p&gt;&lt;bold&gt;MATERIALS AND METHODS.&lt;/bold&gt; The composite collagen-containing hydrogel was provided by «FIRST ALIVE COLLAGEN» LLC (Russia) and is a registered dietary supplement. The work used a commercial culture of human skin fibroblast cells and human duodenal epithelial cells (line HuTu-80). The viability of intestinal cells and fibroblasts was assessed using light and fluorescence microscopy and flow cytometry methods.&lt;/p&gt;&#13;
&lt;p&gt;&lt;bold&gt;RESULTS AND DISCUSSION.&lt;/bold&gt; It has been established that indomethacin inhibits cell growth, causes apoptosis and death of enterocytes, and also leads to the accumulation of cells in the S-phase, which indicates a disruption in the regulation of the cell cycle. It was revealed that collagen hydrogel prevents cell death caused by indomethacin and reduces the number of apoptotic cells in the population. The protective effect of collagen hydrogel is characterized by normalization of the cell cycle of enterocytes and restoration of their growth and proliferative activity.&lt;/p&gt;&#13;
&lt;p&gt;&lt;bold&gt;CONCLUSION.&lt;/bold&gt; Thus, collagen hydrogel, in vitro, is able to reduce the pathogenic effect of indomethacin on human intestinal epithelial cells. The protective effect of collagen hydrogel is characterized by maintaining viability, inhibiting apoptotic processes, and maintaining cell cycle stability. The results obtained indicate the prospects of using a dietary supplement based on a composite collagen hydrogel as a prophylactic agent to reduce the risk of NSAID-associated gastrointestinal diseases. However, to confirm the therapeutic effectiveness of the dietary supplement, further research is necessary, both using experimental animal modeling of NSAID-associated diseases of the human gastrointestinal tract, and clinical studies.&lt;/p&gt;</abstract><kwd-group xml:lang="en"><kwd>collagen hydrogel</kwd><kwd>non-steroidal anti-inflammatory drugs</kwd><kwd>enterocytes</kwd><kwd>HuTu-80</kwd><kwd>apoptosis</kwd><kwd>cell cycle</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>коллагеновый гидрогель</kwd><kwd>нестероидные противовоспалительные препараты</kwd><kwd>энтероциты</kwd><kwd>HuTu-80</kwd><kwd>апоптоз</kwd><kwd>клеточный цикл</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Wongrakpanich S., Wongrakpanich A., Melhado K., Rangaswami J.A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging and disease. 2018; 9(1): 143–150. https://doi.org/10.14336/AD.2017.0306</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Bindu S., Mazumder S., Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochemical Pharmacology. 2020; 180: 114147. https://doi.org/10.1016/j.bcp.2020.114147</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>García-Rayado G., Navarro M., Lanas A. NSAID induced gastrointestinal damage and designing GI-sparing NSAIDs. Expert Review of Clinical Pharmacology. 2018; 11(10): 1031–1043. https://doi.org/10.1080/17512433.2018.1516143</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Boonyong C., Vardhanabhuti N., Jianmongkol S. Natural polyphenols prevent indomethacin-induced and diclofenac-induced Caco-2 cell death by reducing endoplasmic reticulum stress regardless of their direct reactive oxygen species scavenging capacity. The Journal of Pharmacy and Pharmacology. 2020; 72(4): 583–591. https://doi.org/10.1111/jphp.13227</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Bäck M., Yin L., Ingelsson E. Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib. European Heart Journal. 2012; 33(15): 1928–1933. https://doi.org/10.1093/eurheartj/ehr421</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Fiorucci S., Distrutti E. COXIBs, CINODs and H₂S-releasing NSAIDs: current perspectives in the development of safer non steroidal anti-inflammatory drugs. Current Medicinal Chemistry. 2011; 18(23): 3494–3505. https://doi.org/10.2174/092986711796642508</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Badri W., Miladi K., Nazari Q.A., et al. Encapsulation of NSAIDs for inflammation management: Overview, progress, challenges and prospects. Int J Pharm. 2016; 515(1-2): 757–773. https://doi.org/10.1016/j.ijpharm.2016.11.002</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Singh D.P., Borse S.P., Nivsarkar M. A novel model for NSAID induced gastroenteropathy in rats. J Pharmacol Toxicol Methods. 2016; 78: 66–75. https://doi.org/10.1016/j.vascn.2015.11.008</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Satoh H., Amagase K., Takeuchi K. Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats. Journal of Pharmacology and Experimental Therapeutics. 2014; 348(2): 227–235. https://doi.org/10.1124/jpet.113.208991</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>He F., Wu C., Li P., et al. Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation. BioMed Research International. 2018; 2018:9171905. https://doi.org/10.1155/2018/9171905</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Vidal-Lletjós S., Andriamihaja M., Blais A., et al. Dietary Protein Intake Level Modulates Mucosal Healing and Mucosa-Adherent Microbiota in Mouse Model of Colitis. Nutrients. 2019; 11(3): 514. https://doi.org/10.3390/nu11030514</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Rahabi M., Salon M., Bruno-Bonnet C., et al. Bioactive fish collagen peptides weaken intestinal inflammation by orienting colonic macrophages phenotype through mannose receptor activation. European Journal of Nutrition. 2022; 61(4): 2051–2066. https://doi.org/10.1007/s00394-021-02787-7</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Zhu W., Ren L., Zhang L., et al. The Potential of Food Protein-Derived Bioactive Peptides against Chronic Intestinal Inflammation. Mediators of Inflammation. 2020; 2020: 6817156. https://doi.org/10.1155/2020/6817156</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Huang W., Chakrabarti S., Majumder K., et al. Egg-derived peptide IRW inhibits TNF-α-induced inflammatory response and oxidative stress in endothelial cells. Journal of Agricultural and Food Chemistry. 2010; 58(20): 10840–10846. https://doi.org/10.1021/jf102120c</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Oyama M., Hung T., Yoda K., et al. A novel whey tetrapeptide IPAV reduces interleukin-8 production induced by TNF-α in human intestinal Caco-2 cells. Journal of Functional Foods. 2017; 35: 376–383. https://doi.org/10.1016/j.jff.2017.06.001</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Nielsen S.D., Liang N., Rathish H., et al. Bioactive milk peptides: an updated comprehensive overview and database. Critical Reviews in Food Science and Nutrition. 2023. https://doi.org/10.1080/10408398.2023.2240396</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Lee M., Kim D., Park S.H., et al. Fish Collagen Peptide (Naticol) Protects the Skin from Dryness, Wrinkle Formation, and Melanogenesis Both In Vitro and In Vivo. Preventive Nutrition and Food Science. 2022; 27(4): 423–435. https://doi.org/10.3746/pnf.2022.27.4.423</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Daskalaki M.G., Axarlis K., Aspevik T., et al. Fish Sidestream-Derived Protein Hydrolysates Suppress DSS-Induced Colitis by Modulating Intestinal Inflammation in Mice. Marine Drugs. 2021; 19(6): 312. https://doi.org/10.3390/md19060312</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Khatri M., Naughton R.J., Clifford T., et al. The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review. Amino Acids. 2021; 53(10): 1493–1506. https://doi.org/10.1007/s00726-021-03072-x</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Arden N.K., Perry T.A., Bannuru R.R., et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nature Reviews Rheumatology. 2021; 17(1): 59–66. https://doi.org/10.1038/s41584-020-00523-9</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Fuentes J., Brunser O., Atala E., et al. Protection against indomethacin-induced loss of intestinal epithelial barrier function by a quercetin oxidation metabolite present in onion peel: In vitro and in vivo studies. Journal of Nutritional Biochemistry. 2022; 100: 108886. https://doi.org/10.1016/j.jnutbio.2021.108886</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Bhatt A.P., Gunasekara D.B., Speer J., et al. Nonsteroidal Anti-Inflammatory Drug-Induced Leaky Gut Modeled Using Polarized Monolayers of Primary Human Intestinal Epithelial Cells. ACS Infectious Diseases. 2018; 4(1): 46–52. https://doi.org/10.1021/acsinfecdis.7b00139</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Handa O., Takayama S., Mukai R., et al. A review of the mechanism and prophylaxis of acetyl salicylic acid-induced injury of the small intestine. Free Radical Research. 2018; 52(11–12): 1266–1270. https://doi.org/10.1080/10715762.2018.1455003</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Barrioni B.R., de Carvalho S.M., Oréfice R.L., et al. Synthesis and characterization of biodegradable polyurethane films based on HDI with hydrolyzable crosslinked bonds and a homogeneous structure for biomedical applications. Materials Science &amp; Engineering C-Materials for Biological Applications. 2015; 52: 22–30. https://doi.org/10.1016/j.msec.2015.03.027</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Chen P., Chen C., Hu M., et al. S-allyl-L-cysteine protects hepatocytes from indomethacin-induced apoptosis by attenuating endoplasmic reticulum stress. FEBS Open Bio. 2020; 10(9): 1900–1911. https://doi.org/10.1002/2211-5463.12945</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Ahluwalia A., Hoa N., Jones M.K., Tarnawski A.S. NSAID-induced injury of gastric epithelial cells is reversible: roles of mitochondria, AMP kinase, NGF, and PGE2. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2019; 317(6): G862–G871. https://doi.org/10.1152/ajpgi.00192.2019</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Wang Z. Cell Cycle Progression and Synchronization: An Overview. Methods in molecular biology. 2022; 2579: 3–23. https://doi.org/10.1007/978-1-0716-2736-5_1</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Luciani M.G., Campregher C., Fortune J.M., et al. 5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint. Gastroenterology. 2007; 132(1): 221–235. https://doi.org/10.1053/j.gastro.2006.10.016</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Koelink P.J., Mieremet-Ooms M.A., Corver W.E., et al. 5-aminosalicylic acid interferes in the cell cycle of colorectal cancer cells and induces cell death modes. Inflammatory Bowel Diseases. 2010; 16(3): 379–389. https://doi.org/10.1002/ibd.21086</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Nurilmala M., Hizbullah H.H., Karnia E., et al. Characterization and Antioxidant Activity of Collagen, Gelatin, and the Derived Peptides from Yellowfin Tuna (Thunnus albacares) Skin. Marine Drugs. 2020; 18(2): 98. https://doi.org/10.3390/md18020098</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Medina-Medrano J.R., Quiñones-Muñoz T.A., Arce-Ortíz A., et al. Antioxidant Activity of Collagen Extracts Obtained from the Skin and Gills of Oreochromis sp. Journal of Medicinal Food. 2019; 22(7): 722–728. https://doi.org/10.1089/jmf.2019.0013</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Carrasco-Pozo C., Morales P., Gotteland M. Polyphenols protect the epithelial barrier function of Caco-2 cells exposed to indomethacin through the modulation of occludin and zonula occludens-1 expression. Journal of Agricultural and Food Chemistry. 2013; 61(22): 5291–5297. https://doi.org/10.1021/jf400150p</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Yin H., Pan X., Song Z., et al. Protective effect of wheat peptides against indomethacin-induced oxidative stress in IEC-6 cells. Nutrients. 2014; 6(2): 564–574. https://doi.org/10.3390/nu6020564</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Jung E.S., Jang H.J., Hong E.M., et al. The Protective Effect of 5-Aminosalicylic Acid Against Non-Steroidal Anti-Inflammatory Drug-Induced Injury Through Free Radical Scavenging in Small Intestinal Epithelial Cells. Medicina (Kaunas). 2020; 56(10): 515. https://doi.org/10.3390/medicina56100515</mixed-citation></ref></ref-list></back></article>
