ANTIULCER ACTIVITY OF PLACENTAL CRYOEXTRACT IN EXPERIMENTAL INDOMETHACIN-INDUCED ULCEROGENESIS

  • Fedir Hladkykh State Organization "Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine", Kharkiv, Ukraine https://orcid.org/0000-0001-7924-4048
Keywords: cryopreserved placenta extract, nonsteroidal anti-inflammatory drugs, indomethacin, ulcerogenicity, enteroprotection

Abstract

Aim. The side effects associated with the use of indometacin are noted by about 30-60% of patients, therefore, in this context the problem of adverse event rate reduction is still relevant today. Cryopreserved placental extract (CEP) attracted our attention as a means of pathogenetic correction of the ulcerogenic action of indomethacin. The aim of the paper is to characterize the antiulcer activity of cryopreserved placenta extract on a model of indomethacin-induced ulcerogenesis.

Materials and Methods. In vivo experimental studies were performed on 28 nonlinear laboratory male rats weighing 200-220 g. Acute indomethacin-induced gastrointestinal injury was replicated by a single injection of indomethacin at 60 mg/kg in rats. Euthanasia of animals was performed after 4 hours after indomethacin administration.

Results and Discussion. Macroscopic evaluation of the condition of the gastric mucosa showed that all animals had numerous pinpoint hemorrhages, and 49.2% of rats had mild hyperemia and abnormal folding. Evaluation of the condition of the small intestinal mucosa showed that 57.1% of rats injected with indomethacin alone had 11.1±4.1 ulcers per 10 cm of mucosa length. Prophylactic administration of esomeprazole led to a statistically significant (p<0.05) attenuation of the ulcerogenic effect of indomethacin on the gastric mucosa - the mean score of the mucosa was 3.9 times lower than in control rats and was 0.9±0.26.

Conclusions. The combined use of indomethacin and CEP was associated with a 1.9-fold lower ulcer index as compared with rats administered indomethacin only, thus demonstrating the gastroprotective activity of CEP. In contrast to esomeprazole, the introduction of CEP has a pronounced enteroprotective effect, as indicated by the absence of damage to small intestinal mucosa in rats treated with the studied cryoextract and indomethacin.

References

Anikin GS, Stozhkova IV, Kukes VG. NSAIDs: safety from the point of evidence-based medicine. Consilium Medicum. 2017; 19: 28-32. DOI: http://doi.org/10.26442/2075-1753_19.7.2.28-32.

Drini M. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Aust Prescr. 2017; 40 (3): 91-3. DOI: http://doi.org/10.18773/austprescr.2017.037.

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; 4: 253-66. DOI: https://doi.org/10.22141/2308-2097.54. 4.2020.216714.

Lucas S. The Pharmacology of Indomethacin. Headache. 2016; 56 (2): 436-46. DOI: http://dx.doi.org/10.1111/head.12769.

Hladkikh FV Preventive-therapeutic strategies of pharmacocorrection of gastropathy induced by non-steroidal anti-inflammatory drugs. Reviews of clinical pharmacology and drug therapy. 2017; 4: 14-23. DOI: http://dx.doi.org/10.17816/RCF15414-23.

AbdelAziz EY, Tadros MG, Menze ET. The effect of metformin on indomethacin-induced gastric ulcer: Involvement of nitric oxide/Rho kinase pathway. European Journal of Pharmacology. 2021; 892: e173812. DOI: https://doi.org/10.1016/j.ejphar.2020.173812.

El-Ashmawy NE, Khedr EG, El-Bahrawy HA, Selim HM. Nebivolol prevents indomethacin-induced gastric ulcer in rats. Journal of Immunotoxicology. 2016;13(4): 580-9. DOI: https://doi.org/10.3109/1547691X.2016.1142488.

Sen LS, Ozdemir Kumral ZN, Memi G, Ercan F, Yegen BC, Yegen C. The gastroprotective effect of obestatin on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism. Physiology International. 2020; 1: 243-55. DOI: https://doi.org/10.1556/2060. 2020. 00025.

El-Sisi AE, Sokar SS, Abu-Risha SE, Khira DY. The potential beneficial effects of sildenafil and diosmin in experimentally-induced gastric ulcer in rats. Heliyon. 2020; 6 (8): e04761. DOI: https://doi.org/10.1016/j.heliyon.2020.e04761.

Goltsev AN, ed. 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: https://doi.org/10.1155/2018/4837930.

Wei Xie, Xielin Huang, Renpin Chen, Ruru Chen , Tang Li, Wei Wu, Zhiming Huang. Esomeprazole alleviates the damage to stress ulcer in rats through not only its antisecretory effect but its antioxidant effect by inactivating the p38 MAPK and NF-?B signaling pathways. Drug Design, Development and Therapy. 2019; 22(13): 2969-84. DOI: http://doi.org/10.2147/DDDT.S193641.

Stefanov OV. Preclinical studies of drugs: guidelines. Kyiv: Avicenna; 2001. 527 p.

Zharikov AYu, Lorenz SE, Bobrov IP, Mazko ON, Makarova OG. Search for new oligopeptide molecules for pharmacological correction of NSAID-induced gastric ulcer. Biomedicine. 2019; 15 (3): 90-7. DOI: https://doi.org/10.33647/2074-5982-15-3-90-97.

Modlin IM, Hunt RH, Malfertheiner P, Moayyedi P, Quigley EM, Tytgat GN, Tack J, Heading RC, Holtman G, Moss SF. Diagnosis and management of non-erosive reflux disease - the Vevey NERD Consensus Group. Digestion. 2009; 80 (2), 74-88. DOI: https://doi.org/10.1159/000219365.

Schneider NI, Plieschnegger W, Geppert M, Wigginghaus B, Hoess GM, Eherer A, Wolf EM, Rehak P, Vieth M, Langner C. Validation study of the Esohisto consensus guidelines for the recognition of microscopic esophagitis. Human pathology. 2014; 31, 45 (5), 994-1002. DOI: https://doi.org/10.1016/j.humpath.2013.12.013.

Hladkikh FV, Stepaniuk NG, Vernygorodsky SV. Macro- and microscopic study of the effect of 2-phenyl-3-carbetoxy-4-dimethylaminomethyl-5-oxybenzofuran hydrochloride (Vinborone) on gastrotoxicity ibuprofen in experimental rheumatoid arthritis in rats. Trajectory of Science: International Electronic Scientific Journal = Traektori? Nauki = Path of Science. 2017; 10: 7001-7018. DOI: http://dx.doi.org/10.22178/pos.27-8.

Rybolovlev UR, Rybolovlev RS. Dosage of substances for mammals by constants of biological activity. Reports of the USSR Academy of Sciences. 1979; 247 (6): 1513-6.

Published
2021-12-23
How to Cite
Hladkykh, F. (2021). ANTIULCER ACTIVITY OF PLACENTAL CRYOEXTRACT IN EXPERIMENTAL INDOMETHACIN-INDUCED ULCEROGENESIS. Acta Medica Leopoliensia, 27(3-4), 68-83. https://doi.org/10.25040/aml2021.3-4.068