EFFECT OF CELL-FREE CRYOPRESERVED BIOLOGICAL AGENTS ON THE CONTENT OF INDIVIDUAL EICOSANOIDS IN RATS WITH FREUND'S ADJUVANT MODELED ARTHRITIS
DOI:
https://doi.org/10.32782/health-2024.1.4Keywords:
placenta cryoextract, spleen cryoextract, conditioned medium of mesenchymal stem cells, prostaglandins, thromboxane, leukotrienes, autoimmune diseasesAbstract
Rheumatoid arthritis is defined as an inflammatory systemic chronic autoimmune disease that manifests as immune cell infiltration, synovial hyperplasia, pannus formation, and destruction of articular cartilage and bone tissue. Despite its simple definition, inflammation is a complex system of cellular and molecular events, based on a cascade of mediators to obtain specific temporal and spatial responses. Endogenous bioactive lipids are the main mediators of homeostasis, as well as acute and chronic inflammatory processes, participating in the initiation, maintenance, and regression of inflammation. The aim of the work is to characterize the effect of cryoextracts of the placenta (СEP) and spleen (CES), as well as the conditioned medium of mesenchymal stem cells (CM-MSC) on the content of prostaglandin (PG) E2, thromboxane (Tx) B2 and leukotriene (LT) B4 in blood serum on the model of adjuvant arthritis (AA) in shures. Experimental studies were conducted on 42 male rats weighing 200–220 g. AA in rats has all the morphofunctional signs of RA in humans and is accompanied by a typical reaction, the main link of which is T-cell immunity. AA was modeled by subplantar injection of complete Freund's adjuvant (CFA) into the hind right limb at the rate of 0.1 ml per rat. AA treatment was carried out from 14 to 28 days. CEP, CES and CM-MSC were injected intramuscularly with an interval of 2 days (a total of 5 injections), on days 14, 17, 20, 23 and 26, respectively. The development of AA in rats was accompanied by an increase in the level of PGE2 by 34.7% (p<0.01), TxB2 by 72.4% (p<0.001) and LTB4 by 74.7% (p<0.001) compared to the indicators of intact animals, which confirmed the immunoinflammatory nature of the simulated pathology. Against the background of the use of cell-free cryopreserved biological agents, as well as the reference drug diclofenac sodium, a decrease in the level of all studied eicosanoids was noted. The use of cell-free cryopreserved biological agents led to a decrease in the level of the studied eicosanoids in the blood serum of AA rats on the 28th day of the experiment. The most pronounced changes were noted against the background of the introduction of CM-MSC – the level of PGE2 decreased by 24.8% (р<0.05), TxB2 by 30.3% (р<0.01) and LTB4 by 25.6% (р<0.01) relative to the parameters of rats with AA without treatment.
References
Huang J., Fu X., Chen X., Li Z., Huang Y., Liang C. Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis. Front Immunol. 2021. № 12. Р. 686155. https://doi.org/10.3389/fimmu.2021.686155
Chiurchiù V., Leuti A., Maccarrone M. Bioactive Lipids and Chronic Inflammation: Managing the Fire Within. Front Immunol. 2018. № 9. Р. 38. https://doi.org/10.3389/fimmu.2018.00038
Artru F., McPhail M.J.W., Triantafyllou E., Trovato F.M. Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids. Front Immunol. 2022. № 13. Р. 867261. https://doi.org/10.3389/fimmu.2022.867261
Dennis E.A., Norris P.C. Eicosanoid storm in infection and inflammation. Nat Rev Immunol. 2015. № 15(8). Р. 511–523. https://doi.org/10.1038/nri3859
Hladkykh F.V., Chyzh M.O. Nonsteroidal anti-inflammatory drugs: a modern understanding of the mechanisms of damage to the digestive tract, the shortcomings of pathogenetic drugs and prospects for biological therapy of NSAID-induced esophagogastroenterocolonopathy. Gastroenterology. 2020. № 4. Р. 253–266. https://doi.org/10.22141/2308-2097.54.4.2020 .216714
Honda T., Segi-Nishida E., Miyachi Y., Narumiya S. Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis. J Exp Med. 2006. № 203(2). Р. 325–335. https://doi.org/10.1084/jem.20051310
Hirata T., Narumiya S. Prostanoids as regulators of innate and adaptive immunity. Adv Immunol. 2012. № 116. Р. 143–174. https://doi.org/10.1016/B978-0-12-394300-2.00005-3
Chen Q., Muramoto K., Masaaki N., Ding Y., Yang H., Mackey M., Li W., Inoue Y., et al. A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010. № 160(2). Р. 292–310. https://doi.org/10.1111/j.1476-5381.2010.00647.x
Aoki T., Narumiya S. Prostaglandins and chronic inflammation. Trends Pharmacol Sci. 2012. № 33(6). Р. 304–311. https://doi.org/10.1016/j.tips.2012.02.004
Hladkykh F.V. Anti-inflammatory properties of diclofenac sodium on background of its combined use with cryopreserved placenta extract in experiment. Problems of Cryobiology and Cryomedicine. 2021. № 31(4). Р. 364–367. https://doi.org/10.15407/cryo31.04.364
Hladkykh F.V. Current understanding of the immunological basis of rheumatoid arthritis: from post-translational modification of proteins to the use of disease-modifying antirheumatic drugs. Eastern Ukrainian medical journal 2023. № 11(4). Р. 326–336. https://doi.org/10.21272/eumj.2023;11(4):326-336
Freund J. Some aspects of active immunization. Annual Review of Microbiology. 1947. № 1. Р. 291–308. https://doi.org/10.1146/annurev.mi.01.100147.001451
Harold F. Stils, adjuvants and antibody production: dispelling the myths associated with Freund’s complete and other adjuvants, Institute for Laboratory Animal Research Journal. 2005. № 46(3). Р. 280–293. https://doi.org/10.1093/ilar.46.3.280
Stefanov O.V., ed. Preclinical studies of medicinal products: methodical recommendations. Kyiv: Avicenna. 2001. 527 p.
Hladkykh F.V. Nonsteroidal anti-inflammatory drugs: therapeutic and undesirable effects, ways of their optimization. Vinnytsia: Tvoty. 2022. 216 p. https://doi.org/10.46879/2022.1
Shepitko V.I. Structural and functional indicators of the cryopreserved liver and the effect of its transplantation on the morphofunctional state of a number of internal organs: dissertation. Doctor of Medicine: special. 14.01.35 – Cryomedicine, Kharkiv, 2004. 326 p. https://nrat.ukrintei.ua/searchdoc/0504U000610/
Bespalova I.G. Peptide composition and biological action of extracts of cryopreserved pig spleen fragments and piglet skin: thesis. biol. n.: in specialty 03.00.19 – Cryobiology, Kharkiv, 2016. 162 p. https://nrat.ukrintei.ua/searchdoc/0416U004539/
Golubinskaya P.A., Sarycheva M.V., Dolzhikov A.A., Bondarev V.P., Stefanova M.S., Soldatov V.O., Nadezhdin S.V., Korokin M.V., et al. Application of multipotent mesenchymal stem cell secretome in the treatment of adjuvant arthritis and contact-allergic dermatitis in animal models. Pharmacy & Pharmacology. 2020. № 8(6). Р. 416–425. https://doi.org/10.19163/2307-9266-2020-8-6-416-425
Globa V.Yu. Use of cryopreserved cell cultures and neurotrophic factors in experimental infravesical obstruction. Thesis in specialty 222 – Medicine, Kharkiv, 2021. 156 p. https://nrat.ukrintei.ua/searchdoc/0821U100913/
Fereidoni M., Ahmadiani A., Semnanian S., Javan M. An accurate and simple method for measurement of paw edema. Journal of Pharmacological and Toxicological Methods. 2000. № 43(1). Р. 11–14. http://doi.org/10.1016/s1056-8719(00)00089-7
Prokopyuk O.S. Placenta cryopreservation and determination of the mechanisms of its influence on the body of recipients of late ontogenesis (experimental study): Thesis in specialty 14.01.35 – Cryomedicine, Kharkiv, 2011. 351 p. https://nrat.ukrintei.ua/searchdoc/0514U000218/
Galchenko S.E., Shkodovska N.Y., Sandomirsky B.P., Hryshchenko V.I. Patent of Ukraine No. 64381. Method of obtaining extracts of xenogenic organs. Application No. 2003054649. Submitted on May 22, 2003; Publ. 16.02.2004. Bul. No. 2.
Galchenko S.E. Extracts of cryopreserved fragments of xenoorgans: procurement and biological effect. Problems of Cryobiology and Cryomedicine. 2005. № 15(3). Р. 403–406.
Bespalova I.G., Rogoza L.A., Galchenko S.Y., Sandomyrsky B.P. Extracts of cryopreserved fragments of pig spleen and piglet skin affect the healing of cold wounds in rats. Problems of Cryobiology and Cryomedicine. 2015. № 25(2). Р. 151–161. https://doi.org/10.15407/cryo25.02.151
Sandomirsky B.P., Galchenko S.E., Byzov V.V. Preparation, cryopreservation and clinical use of pig spleen fragments and their extract: Methodological recommendations. Ministry of Health of Ukraine; Center for transplantation of organs,tissues and cells; Kharkiv, 2001. 9 p.
Olefirenko L.C. The effect of cryodestruction, extracts of the liver and spleen on regenerative processes in the liver in experimental cirrhosis. Thesis in specialty 14.01.35 – Cryomedicine, Kharkiv, 2008. 101 p. https://nrat.ukrintei.ua/searchdoc/0408U004142/
Nesteruk G.V., Alabedalkarim N.M., Kolot N.V., Komaromi N.A., Protsenko O.S., Legach E.I. The effect of conditioned media from glial cell cultures on the reproductive system of female rats of different ages. Problems of endocrine pathology. 2022. № 79(2). Р. 88–96. https://doi.org/10.21856/j-PEP.2022.2.13
Zar J.H. Biostatistical analysis (5 ed.). Prentice-Hall, Englewood. 2014; 960 р.
Tripathy J.P. Secondary data analysis: ethical issues and challenges. Iranian Journal of Public Health. 2013. № 42(12). Р. 1478–1479.
Yan F., Robert M., Li Y. Statistical methods and common problems in medical or biomedical science research. International Journal of Physiology, Pathophysiology and Pharmacology. 2017. № 9(5). Р. 157–163.
Fattahi M.J., Mirshafiey A. Prostaglandins and rheumatoid arthritis. Arthritis. 2012. № 2012. Р. 239310. https://doi.org/10.1155/2012/239310
Ferrante E., Vazzana N., Santilli F., Di Cicco M., Lauriti C., Di Battista L., Ciabattoni G., Di Matteo L., Davi G. Determinants of thromboxane biosynthesis in rheumatoid arthritis: Role of RAGE and oxidant stress. Free Radic Biol Med. 2010. № 49(5). Р. 857–864.
Zheng L.X., Li K.X., Hong F.F., Yang S.L. Pain and bone damage in rheumatoid arthritis: role of leukotriene B4. Clin Exp Rheumatol. 2019. № 37(5). Р. 872–878.