THERAPEUTIC EFFECTS OF MELATONIN IN AN ETHANOL-INDUCED GASTRIC ULCER MODEL
Introduction. Recently, melatonin and its agonists have been proven to be effective in the treatment of jet lag syndrome, insomnia, stress, fear, anger, anxiety, stress conditions, which are accompanied by sleep disorders, increase the immune system of the whole body, and as antioxidant protection. Melatonin is known to be an important chronobiological molecule that exerts its effect on any system in the body. The role and pharmacological effect of melatonin in the gastrointestinal system is still one of the important topics, and research continues in various directions.
Aim. To monitor the therapeutic effects of melatonin in relation to ethanol concentration in an ethanol-induced experimental gastric ulcer model.
Material’s and method. A prospective preclinical (experimental) single-center study. The work was carried out using laboratory rats. The research work was carried out for each of the 6 groups, in a model of gastric ulcer induced by ethanol of various concentrations (100-75-60%) and melatonin was administered to the ulcer (15 mg/kg) and the control group. The obtained data were subjected to statistical analysis using a trial version of the SPSS statistical program (SPSS 20 Inc, Chicago, IL, USA), the critical significance level (p) was assumed to be 0.05.
Results. In addition to this increase in the wound area, melatonin administered as a prophylactic subcutaneous injection reduced the overall wound area. In the group of wounds induced by ethanol (100%), the wound area was 15.011.92 mm, after intraperitoneal injection of melatonin (15 mg/kg), and after 30 minutes the wound area was 14.011.74 mm in the 100% ethanol-induced group and 13. 241.71 mm, in the 75% ethanol-induced group, 11.871.45 mm in the melatonin + 75% ethanol-induced group, 11.521.15 mm in the 60% ethanol-induced group and 6.12 0.54 mm in the melatonin + 60% ethanol-induced group.
Conclusion. In this study, melatonin showed a positive effect in the prevention and treatment of ethanol-induced ulcers at different concentrations. A significant change was observed at higher levels of melatonin inhibition of ethanol exposure at lower concentrations.
Akbota A. Skenderova1, https://orcid.org/0000-0002-5392-9433
Gulnaz О. Nuskabayeva1, https://orcid.org/0000-0002-2906-1427
Ugilzhan B.Tatykayeva1, https://orcid.org/0000-0002-7519-479X
Gulzat Zh. Sarsenbayeva2, https://orcid.org/0000-0002-1518-6528
Kanatzhan S. Kemelbekov2, https://orcid.org/0009-0008-1619-6278
Aizat A. Seidakhmetova2, https://orcid.org/0000-0002-5794-3814
1. Bubenık George A. Gastrointestinal melatonin: localization, function, and clinical relevance. Digestive diseases and sciences. 2002. №47. P. 2336-2348. DOI:10.1023/a:1020107915919
2. Boutin J.A., Kennaway D.J., Jockers R. Melatonin: Facts, Extrapolations and Clinical Trials. Biomolecules, 2023. 13(6), 943. https://doi.org/10.3390/biom13060943
3. BrzozowskI Tomasz et al. The role of melatonin and L‐tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. Journal of pineal research. 1997. №23(2). P.79-89. DOI:10.1111/j.1600-079x.1997.tb00339.x
4. Carrıllo‐Vıco Antonio et al. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. The FASEB Journal. 2004. №18.3. P. 537-539. DOI:10.1096/fj.03-0694fje
5. Claustrat Bruno, Brun Jocelyne, Chazot Guy. The basic physiology and pathophysiology of melatonin. Sleep medicine reviews, 2005. №9(1). P. 11-24. DOI:10.1016/j.smrv.2004.08.001
6. Conway S, Canning SJ, Howell HE, Mowat ES,Barrett P, Drew JE, et al. Characterisation of human melatonin mt(1) and MT(2) receptors by CRE-luciferasereporter assay. Eur J Pharmacol 2000. 390:15-24.
7. Cruz-Sanabria F., Carmassi C., Bruno S., Bazzani A., Carli M., Scarselli M., Faraguna U. Melatonin as a Chronobiotic with Sleep-promoting Properties. Current neuropharmacology, 2023. 21(4), 951–987. https://doi.org/10.2174/1570159X20666220217152617
8. Choudhary P., Roy T., Chatterjee A., Mishra V.K., Pant S., Swarnakar S. Melatonin rescues swim stress induced gastric ulceration by inhibiting matrix metalloproteinase-3 via down-regulation of inflammatory signaling cascade. Life sciences, 2022. 297, 120426. https://doi.org/10.1016/j.lfs.2022.120426
9. Chang C.L., Chen C.H., Chiang J.Y., Sun C.K., Chen Y.L., et al. Synergistic effect of combined melatonin and adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes on amelioration of dextran sulfate sodium (DSS)-induced acute colitis. American journal of translational research, 2019. 11(5), 2706–2724. PMID: 31217848
10. Faghih Dinevari M., Jafarzadeh F., Jabbaripour Sarmadian A., Abbasian S., Nikniaz Z., Riazi A. The effect of melatonin on irritable bowel syndrome patients with and without sleep disorders: a randomized double-blinded placebo -controlled trial study. BMC gastroenterology, 2023. 23(1), 135. https://doi.org/10.1186/s12876-023-02760-0
11. Grıgg-Damberge, Madeleine M., Ianakieva Dessislava. Poor quality control of over-the-counter melatonin: what they say is often not what you get. Journal of Clinical Sleep Medicine. 2017. №13(2). P. 163-165. DOI: 10.5664/jcsm.6434
12. Hardeland R. Redox Biology of Melatonin: Discriminating Between Circadian and Noncircadian Functions. Antioxidants & redox signaling, 2022. 37(10-12), 704–725. https://doi.org/10.1089/ars.2021.0275
13. Jaworek Jolanta, Brzozowskı Tomasz, Konturek Stanislaw Jan. Melatonin as an organoprotector in the stomach and the pancreas. Journal of pineal research. 2005. №38(2). P.73-83. DOI: 10.1111/j.1600-079X.2004.00179.x
14. Kato K. et al. Circadian rhythm of melatonin and prostaglandin in modulation of stress‐induced gastric mucosal lesions in rats. Alimentary pharmacology & therapeutics. 2002. №16. P.29-34. DOI: 10.1046/j.1365-2036.16.s2.11.x
15. Konturek Peter C. et al. Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis. Journal of pineal research. 2013. № 55 (1). P. 46-57. DOI:10.1111/jpi.12048
16. Konturek S.J. et al. Localization and biological activities of melatonin. J. Physiol. Pharmacol. 2007. №58(3) P. 381-405. PMID:17928638
17. Konturek S.J., et al. Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves. Journal of Physiology and Pharmacology. 2007. №58(2). P. 361. PMID:17622703
18. Mayo J.C., Sainz R.M. Melatonin from an Antioxidant to a Classic Hormone or a Tissue Factor: Experimental and Clinical Aspects 2019. International journal of molecular sciences, 2020. 21(10), 3645. https://doi.org/10.3390/ijms21103645
19. Macchi M.M., Bruce J.N. Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol. 2004. № 25. P. 177-195. https://doi.org/10.1016/j.yfrne.2004.08.001
20. Majka, Jolanta, et al. Melatonin in prevention of the sequence from reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma: experimental and clinical perspectives. International journal of molecular sciences – 2018. №19(7). P. 2033. DOI: 10.3390/ijms19072033
21. Michurina S.V., Kolesnikov S.I., Ishchenko I.Y., Arkhipov S.A. Light-Induced Functional Pinealectomy: Expression of MT2 Receptors in Liver Cells of C57BL/6 Mice after Melatonin Treatment. Bulletin of experimental biology and medicine, 2022. 173(4), 569–574. https://doi.org/10.1007/s10517-022-05590-4
22. Mehrzadi S., Sheibani M., Koosha F., Alinaghian N., Pourhanifeh M.H., Tabaeian S.A.P., Reiter R.J., Hosseinzadeh A. Protective and therapeutic potential of melatonin against intestinal diseases: updated review of current data based on molecular mechanisms. Expert review of gastroenterology & hepatology, 2023. 17(10), 1011–1029. https://doi.org/10.1080/17474124.2023.2267439
23. Özçelık Fatih et al. Melatonin: Genel özellikleri ve psikiyatrik bozukluklardaki rolü. Psikiyatride Güncel Yaklaşımlar. 2013. №5(2). P. 179-203. https://doi.org/10.5455/cap.20130512
24. Pereıra Ricardo de Souza. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. Journal of Pineal Research. 2006. №41(3). P. 195-200. DOI:10.1111/j.1600-079X.2006.00359.x
25. Potes Y., Caballero B. 2023. Special Issue on "Pleiotropic Benefits of Melatonin: From Basic Mechanisms to Disease". International journal of molecular sciences, 24(6), 5223. https://doi.org/10.3390/ijms24065223
26. Peña-Mercado E., Garcia-Lorenzana M., Huerta-Yepez S., Cruz-Ledesma A., Beltran-Vargas N.E. Effect of melatonin on electrical impedance and biomarkers of damage in a gastric ischemia/reperfusion model. PloS one, 2022. 17(8), e0273099. https ://doi.org/10.1371/ journal. pone. 0273099
27. Ratzburg Courtney. Melatonin–the myths and facts. Vanderbilt University. 2007. №12(02). Р.376-384
28. Ruan H., Li X., Zhou L., Zheng Z., Hua R., Wang X., Wang Y., Fan Y., et al. Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure. Science China. Life sciences, 2024. 67(2), 360–378. https://doi.org/10.1007/s11427-022-2365-1
29. Sahoo D.K., Heilmann R.M., Paital B., Patel A., Yadav V.K., Wong D., Jergens A.E. Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease. Frontiers in endocrinology, 2023. 14, 1217165. https://doi.org/10.3389/fendo.2023.1217165
30. Skenderova A., Sebile Koç D., Güvel M.C., Öztürk Fincan G., Uluoğlu C. The role of melatonin and nitric oxide in the neurogenic contraction responses of rat fundus strips to electrical field stimulation in the peptic ulcer model. 26th National and 1st International Pharmacology Congress; Turkish Pharmacology Association, Turkey, 2021.Р.1264-1271
31. Tassan Mazzocco M., Pisanu C., Russo L., Acconcia, C., Cambiaghi M., De Girolamo S., Squassina A., Cherchi L. 2023. Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: A translational study. Pharmacological research, 198, 106993. https://doi.org/10.1016/j.phrs.2023.106993
32. Tordjman Sylvie et al. Melatonin: pharmacology, functions and therapeutic benefits. Current neuropharmacology. 2017. № 15(3). P. 434-443. DOI:10.2174/1570159X14666161228122115
33. Yazıcı Cevat, Kader Köse. Melatonin: karanlığın antioksidan gücü. Sağlık Bilimleri Dergisi. 2004. №13(2). P. 56-66.
34. Zagajewski J., Wojcik-Grzybek D., Brzozowski B., Majka J., et al. Simultaneous detection of melatonin and six metabolites of L-tryptophan pathway in rat gastric mucosa. Journal of physiology and pharmacology: an official journal of the Polish Physiological Society, 2021. 72(6), 10.26402/jpp.2021.6.15.https://doi.org/10.26402/jpp.2021.6.15
Number of Views: 3
Bibliography link
Skenderova A.A., Nuskabayeva G.N., Tatykayeva U.B., Sarsenbayeva G.Zh., Kemelbekov K.S., Seidakhmetova A.A. Therapeutic effects of melatonin in an ethanol-induced gastric ulcer model // Nauka i Zdravookhranenie [Science & Healthcare]. 2024. Vol.26 (5), pp. 85-92. doi 10.34689/SH.2024.26.5.011Related publications:
EMBOLIZATION OF THE UTERINE ARTERIES FOR LATE POSTPARTUM HEMORRHAGE DUE TO METROENDOMETRITIS: A CLINICAL CASE
DESCRIPTION OF A CLINICAL CASE OF GENERALIZED LYMPHADENOPATHY OF UNKNOWN ETIOLOGY
CLINICAL RELEVANCE OF KRAS MUTATION TESTING IN METASTATIC COLORECTAL USING DIFFERENT SEQUENCING PLATFORMS: A CASE REPORT
FIRST EXPERIENCE AND SUCCESSFUL SURGICAL TREATMENT OF LEFT KIDNEY CANCER WITH EXTENDED TUMOR VENOUS THROMBOSIS OF THE INFERIOR VENA CAVITY AND RIGHT ATRIUM [LEVEL IV] IN THE REPUBLIC OF KAZAKHSTAN
PROGNOSTIC SIGNIFICANCE OF GENETIC TUMOR MARKERS IN THYROID NEOPLASMS: LITERATURE REVIEW