An Experimental Study of the Cryopreserved Placenta Extract Effect On the Sodium Diclofenac Anti-Inflammatory Activity
Keywords:cryopreserved placenta extract, exudative inflammation, nonsteroidal anti-inflammatory drugs, diclofenac sodium, carrageenan
Background. As a means of correcting the ulcerogenic effect of nonsteroidal anti-inflammatory drugs, our attention was attracted by a cryopreserved extract of the human placenta, which has a multivector spectrum of biological activity. To date, there is no information about its effect on the specific activity of this class of medicines (anti-inflammatory, analgesic, etc.) in published sources.
Objective. We are aimed to characterize the effect of cryopreserved placenta extract on the anti-inflammatory activity of diclofenac sodium when administered separately in a model of acute exudative inflammation.
Methods. Experimental studies in vivo were conducted on 28 nonlinear male laboratory rats. The model of acute exudative inflammation was reproduced by subplantar injection of 0.1 ml of 1.0% aqueous solution of λ-karagenin into the right hind limb of rats. Cryopreserved placenta extract was administered intramuscularly at a dose of 0.16 ml/kg 60 minutes before diclofenac sodium (8 mg/kg).
Results. Preventive administration of diclofenac sodium caused an antiexudative effect as early as 30 minutes after administration of λ-karagenin – its anti-inflammatory activity was 11.0%, which is 4.6 times higher than similar indicators at the same time in rats injected with placental cryoextract. At 60 minutes of observation, diclofenac sodium was comparable in anti-inflammatory activity with cryopreserved placenta extract: 28.6% and 22.2%, respectively, but at 120 and 180 minutes, diclofenac sodium exceeded the studied cryoextract in antiphlogistic effect by 1.6 times in both periods of observation. The anti-inflammatory effect of the combined separate administration of placenta cryoextract and diclofenac sodium before λ-karagenin for 30 and 60 minutes was 12.7% and 32.3%, respectively, which is comparable with analogous indicators against the background of diclofenac sodium monotherapy. However, at 120 minutes of observation, the group of combined use of placenta cryoextract and diclofenac sodium showed the greatest anti-inflammatory effect among rats of all the studied groups – 52.6%, which was 2.2 times higher than the indicators of the placenta cryoextract monotherapy group and 1.4 times lower than the indicators of the rats of the diclofenac sodium monotherapy group.
Conclusions. 4 hours after administration, placental cryoextract had a suppressive effect on kinins like diclofenac sodium, and in the prostaglandin period of caragenin-induced inflammation against the background of combined use of the studied cryoextract and diclofenac sodium, the anti-inflammatory activity was 46.4 %. This suggests a suppressive effect on the production of prostaglandins as a possible mechanism of anti-exudative action of cryopreserved placenta extract.
Zhuravlyova LV, Oliynyk MO. NSAID induced gastropathy in the practice of a family doctor. Modern Gastroenterol. 2018;3(101):48-53. DOI: 10.30978/MG-2018-3-48
Bacchi S, Palumbo P, Sponta A, Coppolino MF. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Antiinflamm Antiallergy Agents Med Chem. 2012;11(1):52-64. DOI: 10.2174/187152312803476255
Karateev AE, Nasonov EL, Ivashkin VT, Martynov AI, Yakhno NN, Arutyunov GP, et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical recommendations. Rheumatol Sci Pract. 2018;56:1-29. DOI: 10.14412/1995-4484-2018-1-29
Hladkykh FV. Preventive and treatment strategies for pharmacocorrection of gastropathy induced by nonsteroidal anti-inflammatory drugs. Rev Clin Pharmacol Drug Ther. 2017;4:14-23. DOI: 10.17816/RCF15414-23
Chorbinskaya SA, Kudryavtseva NA, Stepanova II, Baryshnikova GA, Alexandrova EB. NSAID-induced gastrointestinal complications. New opportunities of gastrointestinal protection. Kremlin Med J. 2019;4:98-104. DOI: 10.26269/brbt-1q23
Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. ACCF/ACG/AHA 2008 Expert Consensus Document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Circulation. 2008;118(8):1894-909. DOI: 10.1161/circulationaha.108.191087
Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020;180:114-47. DOI: 10.1016/j.bcp.2020.114147
Bondarenko OO, Agibalov OM. The drug-induced injury of the upper gastrointestinal tract: prophylaxis and treatment. Modern Gastroenterol. 2019;2(106):55-65. DOI: 10.30978/MG-2019-2-55
Hladkykh FV, Chyzh MO. 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;54(4):253-66. DOI: 10.22141/2308-2097.54.4.2020.216714
Karateev AE. Modification of traditional NSAIDs as a method to increase their safety and ease of use. Rus Med J. 2015;7:392-6.
Hladkykh FV, Stepaniuk NH. Characteristics of anti-inflammatory and analgesic activity of ibuprofen and its combination with vinboron in a model of adjuvant arthritis in rats. Visnyk Naukovykh Doslidzhen. 2015;2(79):108-11. DOI: 10.11603/2415-8798.2015.2.5617
Hladkykh FV, Stepaniuk NG. Description of the therapeutic effect of ibuprofen and its combination with vinboron according to hematological parameters in the model of adjuvant arthritis in rats. Lviv Med J. 2015;4:64-70.
Ercan N, Uludag MO, Agis ER, D-Yilmaz E. The anti-inflammatory effect of diclofenac is considerably augmented by topical capsaicinoids-containing patch in carrageenin-induced paw oedema of rat. Inflammopharmacology. 2013;21(6):413-9. DOI: 10.1007/s10787-013-0175-7
Goltsev AN, editor. Placenta: cryopreservation, clinical use. Kharkiv; 2013. 268 p.
Pogozhykh O, Prokopyuk V, Figueiredo C, Pogozhykh D. Placenta and placental derivatives in regenerative therapies: experimental studies, history, and prospects. Stem Cells International. 2018;2018:1-14. DOI: 10.1155/2018/4837930
Hladkykh FV, Chyzh MO. Modulation of meloxicam-induced changes in gastrointestinal and motor activity of the stomach by applying placenta cryoextract. Proc Shevchenko Sci Soc Med Sci. 2021;64(1):84-94. DOI: 10.25040/ntsh2021.01.08
Hladkykh FV, Chyzh MO. Modes of administration and antiulcer activity of cryopreserved placenta extract in gastropathies induced by nonsteroidal anti-inflammatory drugs. In: Proceedings of the 45th Annual Conference of Young Scientists Cold in Biology and Medicine: Current Issues in Cryobiology, Transplantology and Biotechnology – 2021; 2021; Kharkiv. Kharkiv: Institute of Cryobiology Problems of the National Academy of Sciences of Ukraine; 2021. p. 26.
Stefanov OJ, editor. Preclinical studies of drugs. Kyiv: Avicenna; 2001. 527 p.
Drogovoz SM, Belyk GV, Demyanenko DV, Kudina OV, Mohammad RD. Screening pharmacological studies of liquefied gas extracts in linden blossoms. Pharmaceut J. 2012;5:94-100.
Sigidin YA, Schwartz GYa, Arzamastsev AP, Lieberman SS, editors. Drug therapy of the inflammatory process: experimental and clinical pharmacology of anti-inflammatory drugs. Moscow: Medicine; 1988. 240 p.
Rybolovlev YuR, Rybolovlev RS. Dosage of substances for mammals by constants of biological activity. Reports of the USSR Academy of Sciences. 1979;247(6):1513-6.
Di Rosa M, Sorrentino L. The mechanism of the inflammatory effect of carrageenin. Europ J Pharmacol. 1968;4:340-3.
Fereidoni M, Ahmadiani A, Semnanian S, Javan M. An accurate and simple method for measurement of paw edema. J Pharmacol Toxicolog Methods. 2000;43(1):11-4. DOI: 10.1016/s1056-8719(00)00089-7
Korang LA, Derymedvid LV. Anti-exudative properties of liquid alcohol-water extract of sweet flag leaves (Acorus Calamus L.). Pharmacol Drug Toxicol. 2019;13(4):263-9. DOI: 10.33250/13.04.263
Gryshchenko NG, Klimenko NA, Gorgol NI, Tatarko SV. Effect of placental cryoextract on chronic inflammation of the ovaries in mice. Medicine Today and Tomorrow. 2010;2-3:7-17.
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