Download full text in PDF
Bìol. Tvarin. 2023; 25 (4): 44–50.
https://doi.org/10.15407/animbiol25.04.044
Received 14.10.2023 ▪ Revision 21.11.2023 ▪ Accepted 25.12.2023 ▪ Published online 29.12.2023
Effect of 4-thiazolidinone derivative and nimesulide on parietal intestinal microbiota of rats during induced inflammation process in vivo
T. Rumynska1,2, G. Lavryk1
This email address is being protected from spambots. You need JavaScript enabled to view it.
1Danylo Halytsky Lviv National Medical University, 69 Pekarska str., Lviv 79010, Ukraine
2Institute of Animal Biology NAAS, 38 V. Stus str., Lviv 79034, Ukraine
Nonsteroidal anti-inflammatory drugs, which are widely used in the treatment of diseases accompanied by pain and fever, can cause diseases of the gastrointestinal tract and are associated with disturbances of the intestinal microbiota. The search for new compounds that could affect the community of microorganisms, exhibiting antimicrobial and anti-inflammatory effects, is an important task of modern medicine and veterinary medicine. One of the promising molecules that have such effects are 4-thiazolidinone derivatives. The aim of this study was to analyze the effect of the newly synthesized compound Les6490 and drug nimesulide on the intestinal wall microbiota of rats in vivo under the conditions of Freund’s adjuvant-induced inflammatory process. The study of the effect of the above-mentioned drugs on the intestinal microbiota in vivo was carried out on a biomodel of rats, which were intragastrically administered with the test substances for two weeks. The study material was the parietal mucos of the small intestine, the microbiome of which was studied using 16S rRNA sequencing. Metagenomic analysis made it possible to analyze the types of microorganisms in experimental groups with induced inflammation (groups A and AL) and without it (groups K, L, N). It was established that the composition of the microbiome of the intestinal tract of rats changes under the conditions of induced inflammation and under the action of the compound Les6490 (groups A and L) in comparison with the control group (group K). The influence of Les6490 on the intestinal tract microbiome composition in rats is similar to that of nimesulide, but the effect is more pronounced. The compound Les6490 potentiates the growth of Helicobacter and has an effect against Stenotrophomonas in the group without induced inflammation (group L), but in the group of inflammation (group AL) no such effect is observed. The compound alone (not in inflammation models) leads to increased species diversity of the rat gut microbiome.
Key words: microbiome, inflammatory process, 4-thiazolidinone derivative, 16S rRNA sequencing, intestinal microbiota, rats
- Anachad O, Taouil A, Taha W, Bennis F, Chegdani F. The implication of short-chain fatty acids in obesity and diabetes. Insights. 2023; 16. DOI: 10.1177/11786361231162720.
- Ather AQ, Tahir MN, Khan MA, Mehmood K, Chaudhry F. 1,3-Diphenyl-1H-pyrazole-4-carbaldehyde. Acta Cryst. 2010; 66 (12): o3170. DOI: 10.1107/S1600536810045630.
- Bander ZA, Nitert MD, Mousa A, Naderpoor N. The gut microbiota and inflammation: An overview. IJERPH, 2020; 17 (20): 7618. DOI: 10.3390/ijerph17207618.
- Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J, Nelson H, Matteson EL, Taneja V. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016; 8 (1): 43. DOI: 10.1186/s13073-016-0299-7.
- Dong Y, Yao J, Deng Q, Li X, He Y, Ren X, Zheng Y, Song R, Zhong X, Ma J, Shan D, Lv F, Wang X, Yuan R, She G. Relationship between gut microbiota and rheumatoid arthritis: A bibliometric analysis. Immunol. 2023; 14. DOI: 10.3389/fimmu.2023.1131933.
- Eissa MM, Mostafa DK, Ghazy AA, El azzouni MZ, Boulos LM, Younis LK. Anti-arthritic activity of Schistosoma mansoni and Trichinella spiralis derived-antigens in adjuvant arthritis in rats: Role of FOXP3+ Treg Cells. PLoS One. 2016; 11: e0165916. DOI: 10.1371/journal.pone.0165916.
- Engevik MA, Danhof HA, Ruan W, Engevik AC, Chang-Graham AL, Engevik KA, Shi Z, Zhao Y, Brand CK, Krystofiak ES, Venable S, Liu X, Hirschi KD, Hyser JM, Spinler JK, Britton RA, Versalovic J. Fusobacterium nucleatum secretes outer membrane vesicles and promotes intestinal inflammation. 2021; 12 (2): e02706-20. DOI: 10.1128/mBio.02706-20.
- Goodrich JK, Davenport ER, Clark AG, Ley RE. The relationship between the human genome and microbiome comes into view. Rev. Genet. 2017; 51: 413–433. DOI: 10.1146/annurev-genet-110711-155532.
- He J, Chu Y, Li J, Meng Q, Liu Y, Jin J, Wang Y, Wang J, Huang B, Shi L, Shi X, Tian J, Zhufeng Y, Feng R, Xiao W, Gan Y, Guo J, Shao C, Su Y, Hu F, Sun X, Yu J, Kang Y, Li Z. Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis. Adv. 2022; 8 (6): eabm1511. DOI: 10.1126/sciadv.abm1511.
- Ivasechko I, Yushyn I, Roszczenko P, Senkiv J, Finiuk N, Lesyk D, Holota S, Czarnomysy R, Klyuchivska O, Khyluk D, Kashchak N, Gzella A, Bielawski K, Bielawska A, Stoika R, Lesyk R. Development of novel pyridine-thiazole hybrid molecules as potential anticancer agents. Molecules. 2022; 27 (19): 6219. DOI: 10.3390/molecules27196219.
- Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, Patel B, Mazzola MA, Liu S, Glanz BL, Cook S, Tankou S, Stuart F, Melo K, Nejad P, Smith K, Topçuolu BD, Holden J, Kivisäkk P, Chitnis T, De Jager PL, Quintana FJ, Gerber GK, Bry L, Weiner HL. Alterations of the human gut microbiome in multiple sclerosis. Commun. 2016; 7: 12015. DOI: 10.1038/ncomms12015.
- Kamel KM, Gad AM, Mansour SM, Safar MM, Fawzy HM. Venlafaxine alleviates complete Freund’s adjuvant-induced arthritis in rats: Modulation of STAT-3/IL-17/RANKL axis. Life Sci. 2019; 226: 68–76. DOI: 10.1016/j.lfs.2019.03.063.
- Konechnyi Y, Lozynskyi A, Ivasechko I, Dumych T, Paryzhak S, Hrushka O, Partyka U, Pasichnyuk I, Khylyuk D, Lesyk R. 3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid as a potential polypharmacological agent. Pharm. 2023; 91 (1): 13. DOI: 10.3390/scipharm91010013.
- Li G, Lin J, Zhang C, Gao H, Lu H, Gao X, Zhu R, Li Z, Li M, Liu Z. Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut Microb. 2021; 13 (1): 1968257. DOI: 10.1080/19490976.2021.1968257.
- López P, de Paz B, Rodríguez-Carrio J, Hevia A, Sánchez B, Margolles A, Suárez A. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Rep. 2016; 6: 24072. DOI: 10.1038/srep24072.
- Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Rev. Microbiol. 2014; 12: 661–672. DOI: 10.1038/nrmicro3344.
- Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. New Engl. J. Med. 2016; 375 (24): 2369–2379. DOI: 10.1056/NEJMra1600266.
- Mitrea L, Nemeş SA, Szabo K, Teleky BE, Vodnar DC. Guts imbalance imbalances the brain: A review of gut microbiota association with neurological and psychiatric disorders. Med. 2022; 9: 813204. DOI: 10.3389/fmed.2022.813204.
- Morrison KE, Jašarević E, Howard CD, Bale TL. It’s the fiber, not the fat: significant effects of dietary challenge on the gut microbiome. Microbiome. 2020; 8 (1): 15. DOI: 10.1186/s40168-020-0791-6.
- NIMESULIDE: instruction, use of NIMESULIDE 100 mg. Normative and directive documents of the Ministry of Health of Ukraine. Available at: https://mozdocs.kiev.ua/likiview.php?id=228
- Nishida Y, Adachi K, Kasai H, Shizuri Y, Shindo K, Sawabe A, Komemushi S, Miki W, Misawa N. Elucidation of a carotenoid biosynthesis gene cluster encoding a novel enzyme, 2,2'-beta-hydroxylase, from Brevundimonas strain SD212 and combinatorial biosynthesis of new or rare xanthophylls. Appl. Environ. Microbiol. 2005; 71 (8): 4286–4296. DOI: 10.1128/AEM.71.8.4286-4296.2005.
- Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A. The genus alistipes: Gut bacteria with emerging implications to inflammation, cancer, and mental health. Immunol. 2020; 11: 906. DOI: 10.3389/fimmu.2020.00906.
- Patil KR, Mahajan UB, Unger BS, Goyal SN, Belemkar S., Surana SJ, Ojha S, Patil CR. Animal models of inflammation for screening of anti-inflammatory drugs: Implications for the discovery and development of phytopharmaceuticals. 2019; 20 (18): 4367. DOI: 10.3390/ijms20184367.
- Patil KR, Patil CR. Anti-inflammatory activity of bartogenic acid containing fraction of fruits of Barringtonia racemosa in acute and chronic animal models of inflammation. J. Tradit. Complement. Med. 2016; 7 (1): 86–93. DOI: 10.1016/j.jtcme.2016.02.001.
- Ram M, Barzilai O, Shapira Y, Anaya JM, Tincani A, Stojanovich L, Bombardieri S, Bizzaro N, Kivity S, Agmon Levin N, Shoenfeld Y. Helicobacter pylori serology in autoimmune diseases — fact or fiction? Chem. Lab. Med. 2013; 51 (5): 1075–1082. DOI: 10.1515/cclm-2012-0477.
- Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK. The toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011; 332 (6032): 974–977. DOI: 10.1126/science.1206095.
- Said MS, Tirthani E, Lesho E. Stenotrophomonas Maltophilia. In: StatPearls. Treasure Island, StatPearls Publ., 2024. Available at: https://www.ncbi.nlm.nih.gov/books/NBK572123
- Salvi PS, Cowles RA. Butyrate and the intestinal epithelium: Modulation of proliferation and inflammation in homeostasis and disease. Cells. 2021; 10 (7): 1775. DOI: 10.3390/cells10071775.
- Sonnenberg A. Protective role of Helicobacter pylori against inflammatory bowel disease: a hypothesis. Gastroenterol. 2009; 33: 23–33. Available at: https://www.ficomputing.net/pdf/September09/SonnenbergArticle.pdf
- Sonnenberg A. Review article: historic changes of Helicobacter pylori-associated diseases. Aliment Pharmacol. Ther. 2013; 38 (4): 329–342. DOI: 10.1111/apt.12380.
- Telesford KM, Yan W, Ochoa-Reparaz J, Pant A, Kircher C, Christy MA, Begum-Haque S, Kasper DL, Kasper LH. A commensal symbiotic factor derived from bacteroides fragilis promotes human CD39+Foxp3+ T cells and treg Gut Microb. 2015; 6 (4): 234–242. DOI: 10.1080/19490976.2015.1056973.
- Turkevych NM, Vvedenskij VM, Petlichnaya LP. Method of obtaining pseudothiohydantoin and thiazolidinedione-2,4. Khim. Zh. 1961; 27: 680–681. Reprinted in: Chem. Abstr. 1962; 56: 73455.
- Wang X, Tang Q, Hou H, Zhang W, Li M, Chen D, Gu Y, Wang B, Hou J, Liu Y, Cao H. Gut microbiota in NSAID enteropathy: New insights from inside. Cell. Infect. Microbiol. 2021; 11: 679396. DOI: 10.3389/fcimb.2021.679396.
- Wehkamp J, Fellermann K, Herrlinger KR, Bevins CL, Stange EF. Mechanisms of disease: defensins in gastrointestinal diseases. Clin. Pract. Gastroenterol. Hepatol. 2005; 2: 406–415. DOI: 10.1038/ncpgasthep0265.
- Yang H, Cai R, Kong Z, Chen Y, Cheng C, Qi S, Gu B. Teasaponin ameliorates murine colitis by regulating gut microbiota and suppressing the immune system response. Med. 2020; 7: 584369. DOI: 10.3389/fmed.2020.584369.
- Yin Z, Liu X, Qian C, Sun L, Pang S, Liu J, Li W, Huang W, Cui S, Zhang C, Song W, Wang D, Xie Z. Pan-genome analysis of Delftia tsuruhatensis reveals important traits concerning the genetic diversity, pathogenicity, and biotechnological properties of the species. Spectr. 2022; 10 (2): e0207221. DOI: 10.1128/spectrum.02072-21.
- Yushyn I, Holota S, Ivantsiv O, Lesyk R. rel-2-[4-Chloro-2-[(5R,6R,7S)-6-[5-(4-methoxyphenyl)-3-(2-naphthyl)-3,4-dihydropyrazole-2-carbonyl]-5-methyl-2-oxo-3,5,6,7-tetrahydrothiopyrano[2,3-d]thiazol-7-yl]phenoxy]acetic acid. Molbank. 2022; 2022: M1410. DOI: 10.3390/M1410.
- Zhao T, Wei Y, Zhu Y, Xie Z, Hai Q, Li Z, Qin, D. Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities. Immunol. 2022; 13: 1007165. DOI: 10.3389/fimmu.2022.1007165.