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The ameliorative effects of melatonin on acetic acid-induced gastric ulcer in rats via its modulatory effects on gut microbiota

Year 2021, Volume: 46 Issue: 1, 186 - 200, 31.03.2021

Abstract

Purpose: The aim of this study was o observe the possible protective effects of melatonin pretreatment on oxidative damage and microbiota alteration due to gastric ulcer in rats.
Materials and Methods: Wistar-albino rats were given (n=32) melatonin (4 mg/kg/day), antibiotic mixture (AB; 1g/L ampicillin + 1g/L neomycin + 1g/L metronidazole), melatonin+AB in drinking water for 12 days or tap water for 15 days (control group; n=8). Subsequently, ulcer was induced. All treatments were continued for three days. Gastric tissues were obtained for biochemical and histopathological examinations, and fecal samples from the rectum were stored for bacteriological measurements.
Results: MPO and MDA levels were increased in untreated ulcer groups compared to the control group. In addition, the levels of luminol-lucigenin chemiluminescence (CL) and 8-OHdG and TNF-α and IL-8 protein expressions were also increased, while TNF-α, IL-8, MDA, 8-OHdG, luminol and lucigenin CL levels were significantly decreased in the melatonin-treated ulcer groups. However, melatonin+AB pretreatment increased antioxidant GSH levels and anti-inflammatory IL-10 levels, and suppressed caspase-3 activity and reduced MPO back to control level..
Conclusion: We anticipate that melatonin treatment, which is an effective antioxidant and radical scavenger, can accelerate ulcer healing along with antibiotics and increase the variety of bacteria impaired by antibiotics in the colon.

References

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Melatoninin bağırsak mikrobiyotasını düzenleyici etkileri aracılığıyla sıçanlarda asetik asitle oluşturulmuş mide ülserinde hafifletici etkileri

Year 2021, Volume: 46 Issue: 1, 186 - 200, 31.03.2021

Abstract

maç: Bu çalışmda melatonin ön-tedavisinin, sıçanlarda mide ülserine bağlı gerçekleşen mikrobiyota değişimine ve oksidatif hasara karşı koruyucu etkilerini araştırmak hedeflenmiştir.
Gereç ve Yöntem: Wistar albino sıçanlara (n=32) 12 gün boyunca içme suyu, melatonin (4mg/kg/gün), antibiyotik karışımı (AB; 1 g/L ampisilin + 1 g/L neomisin+ 1 g/L metronidazol), melatonin+ AB içme suyunda verildi. Ardından ülser oluşturuldu. Katkısız içme suyu alan sıçanların yarısına cerrahi işlem yapıldı ama asetik asit uygulanmadı (kontrol grubu; n=8). Cerrahi sonrasındaki 3 gün boyunca uygulanan tüm tedavilere devam edildi. Mide dokuları biyokimyasal ve histopatolojik incelemeler için çıkarıldı. Rektumdan alınan fekal örnekler bakteriyolojik ölçümler için uygun koşullarda saklandı.
Bulgular: Tedavi almayan ülser grubunun mide dokusunda MDA, MPO, 8-OHdG, luminol ve lusigenin kemilüminesans seviyeleri, TNF-α ve IL-8 protein ekspresyonları kontrol grubuna göre anlamlı derecede artarken, antioksidan GSH seviyesinin azaldığı gözlendi. Melatonin+AB ön-tedavi uygulaması antioksidan GSH seviyesini ve anti-inflamatuvar IL-10 miktarını artırmış, kaspaz-3 aktivitesini baskılamış ve dokuya nötrofil göçünü kontrol düzeyine inecek şekilde azaltmıştır.
Sonuç: Etkin bir antioksidan ve radikal süpürücü olan melatoninin antibiyotik ile birlikte verilmesinin, ülser iyileşmesini hızlandırmada ve kolondaki dağılımı bozulan bakteriyel çeşitliliği düzeltmede daha etkili olacağı öngörülmektedir.

Supporting Institution

YOK

References

  • 1. Najm WI. Peptic ulcer disease. Primary Care: Clinics in Office Practice. 2011;38:383-94.
  • 2. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology. 2008;135:41-60.
  • 3. Chan FK, Leung W. Peptic-ulcer disease. The Lancet. 2002;360:933-41.
  • 4. da Silva LM, Pezzini BC, Somensi LB, Mariano LNB, Mariott M, Boeing T, et al. Hesperidin, a citrus flavanone glycoside, accelerates the gastric healing process of acetic acid-induced ulcer in rats. Chemico-biological interactions. 2019;308:45-50.
  • 5. Chung KT, Shelat VG. Perforated peptic ulcer-an update. World journal of gastrointestinal surgery. 2017;9:1.
  • 6. Chen C-Q, Fichna J, Bashashati M, Li Y-Y, Storr M. Distribution, function and physiological role of melatonin in the lower gut. World journal of gastroenterology: WJG. 2011;17:3888.
  • 7. Reiter RJ, Maestroni GJ. Melatonin in relation to the antioxidative defense and immune systems: possible implications for cell and organ transplantation. Journal of molecular medicine. 1999;77:36-9.
  • 8. Rodriguez C, Mayo JC, Sainz RM, Antolín I, Herrera F, Martín V, et al. Regulation of antioxidant enzymes: a significant role for melatonin. Journal of pineal research. 2004;36:1-9.
  • 9. Tan D-X. Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocr j. 1993;1:57-60.
  • 10. Bandyopadhyay D, Ghosh G, Bandyopadhyay A, Reiter RJ. Melatonin protects against piroxicam‐induced gastric ulceration. Journal of pineal research. 2004;36:195-203.
  • 11. Celinski K, Konturek P, Konturek S, Slomka M, Cichoz-Lach H, Brzozowski T, et al. Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans. Journal of Physiology and Pharmacology. 2011;62:521.
  • 12. Konturek S, Konturek P, Brzozowski T. Melatonin in gastroprotection against stress-induced acute gastric lesions and in healing of chronic gastric ulcers. Journal of physiology and pharmacology. 2006;57:51.
  • 13. Mohamadin AM, Ashour OM, El‐Sherbeny NA, Alahdal AM, Morsy GM, Abdel‐Naim AB. Melatonin protects against hydrogen peroxide‐induced gastric injury in rats. Clinical and Experimental Pharmacology and Physiology. 2009;36:367-72.
  • 14. Xu H, Wang X, Feng W, Liu Q, Zhou S, Liu Q, et al. The gut microbiota and its interactions with cardiovascular disease. Microbial Biotechnology. 2020;13:637-56.
  • 15. Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, et al. Structure, function and diversity of the healthy human microbiome. nature. 2012;486:207.
  • 16. Walsh J, Griffin BT, Clarke G, Hyland NP. Drug–gut microbiota interactions: implications for neuropharmacology. British journal of pharmacology. 2018;175:4415-29.
  • 17. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. The lancet Diabetes & endocrinology. 2015;3:207-15.
  • 18. Kamada N, Seo S-U, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nature Reviews Immunology. 2013;13:321-35.
  • 19. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262-7.
  • 20. Chan FK, To K, Wu JC, Yung M, Leung W, Kwok T, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial. The Lancet. 2002;359:9-13.
  • 21. Jia W, Li H, Zhao L, Nicholson JK. Gut microbiota: a potential new territory for drug targeting. Nature reviews Drug discovery. 2008;7:123-9.
  • 22. Marshall B, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The lancet. 1984;323:1311-5.
  • 23. Walsh JH, Peterson WL. The treatment of Helicobacter pylori infection in the management of peptic ulcer disease. New England Journal of Medicine. 1995;333:984-91.
  • 24. Guevara B, Cogdill AG. Helicobacter pylori: A Review of Current Diagnostic and Management Strategies. Digestive Diseases and Sciences. 2020:1-15.
  • 25. Bühling A, Radun D, Müller W, Malfertheiner P. Influence of anti‐Helicobacter triple‐therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora. Alimentary pharmacology & therapeutics. 2001;15:1445-52.
  • 26. Lou J-g, Jie C, Huang X-l, Zhao Z-y. Changes in the intestinal microflora of children withHelicobacter pyloriinfection and afterHelicobacter pylorieradication therapy. Chinese medical journal. 2007;120:929-31.
  • 27. Wu L, Wang Z, Sun G, Peng L, Lu Z, Yan B, et al. Effects of anti-H. pylori triple therapy and a probiotic complex on intestinal microbiota in duodenal ulcer. Scientific reports. 2019;9:1-11.
  • 28. Yildirim A, Tamer SA, Sahin D, Bagriacik F, Kahraman MM, Onur ND, et al. The effects of antibiotics and melatonin on hepato-intestinal inflammation and gut microbial dysbiosis induced by a short-term high-fat diet consumption in rats. British Journal of Nutrition. 2019;122:841-55.
  • 29. Gürler EB, Çilingir‐Kaya ÖT, Peker Eyüboglu I, Ercan F, Akkiprik M, Reiter RJ, et al. Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats. Cell biochemistry and function. 2019;37:102-12.
  • 30. Carvalho B, Guadagnini D, Tsukumo D, Schenka A, Latuf-Filho P, Vassallo J, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia. 2012;55:2823-34.
  • 31. Okabe S, JLA R. Pfeiffer CJ. A method for experimental, pen-etrating gastric and duodenal ulcer in rats. Am J Dig Dis. 1971;16:277-84.
  • 32. Casini A, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. The American journal of pathology. 1986;123:520.
  • 33. Aykaç G, Uysal M, Yalçin AS, Koçak-Toker N, Sivas A, Öz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology. 1985;36:71-6.
  • 34. Bradley P, Da P. Christensen RD, Rothstein G: Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J invest Dermatol. 1982;78:206-9.
  • 35. Haklar G, Ulukaya‐Durakbaś Ç, Yüksel M, Dagh T, Yalcin A. Oxygen radicals and nitric oxide in rat mesenteric ischaemia‐reperfusion: Modulation by L‐arginine and NG‐nitro‐L‐arginine methyl ester. Clinical and experimental pharmacology and physiology. 1998;25:908-12.
  • 36. Arabacı Tamer S, Üçem S, Büke B, Güner M, Karaküçük AG, Yiğit N, et al. Regular moderate exercise alleviates gastric oxidative damage in rats via the contribution of oxytocin receptors. The Journal of Physiology. 2020.
  • 37. Matsuzaki J, Suzuki H, Nishizawa T, Hirata K, Tsugawa H, Saito Y, et al. Efficacy of sitafloxacin-based rescue therapy for Helicobacter pylori after failures of first-and second-line therapies. Antimicrobial agents and chemotherapy. 2012;56:1643-5.
  • 38. Boltin D. Probiotics in Helicobacter pylori-induced peptic ulcer disease. Best Practice & Research Clinical Gastroenterology. 2016;30:99-109.
  • 39. Oh B, Kim BS, Kim JW, Kim JS, Koh SJ, Kim BG, et al. The effect of probiotics on gut microbiota during the Helicobacter pylori eradication: randomized controlled trial. Helicobacter. 2016;21:165-74.
  • 40. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620-33.
  • 41. Makobongo MO, Einck L, Peek Jr RM, Merrell DS. In vitro characterization of the anti-bacterial activity of SQ109 against Helicobacter pylori. PloS one. 2013;8:e68917.
  • 42. Memariani Z, Sharifzadeh M, Bozorgi M, Hajimahmoodi M, Farzaei MH, Gholami M, et al. Protective effect of essential oil of Pistacia atlantica Desf. On peptic ulcer: role of α-pinene. Journal of Traditional Chinese Medicine. 2017;37:57-63.
  • 43. Park H, Cho D, Huang E, Seo JY, Kim WG, Todorov SD, et al. Amelioration of Alcohol Induced Gastric Ulcers Through the Administration of Lactobacillus plantarum APSulloc 331261 Isolated From Green Tea. Frontiers in microbiology. 2020;11:420.
  • 44. Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Digestive diseases and sciences. 2005;50:S24-S33.
  • 45. Naito Y, Yoshikawa T, Matsuyama K, Nishimura S, Yagi M, Kondo M. Effects of free radical scavengers on indomethacin-induced aggravation of gastric ulcer in rats. Digestive diseases and sciences. 1995;40:2019-21.
  • 46. Takeuchi K, Ueshima K, Hironaka Y, Fujioka Y, Matsumoto J, Okabe S. Oxygen free radicals and lipid peroxidation in the pathogenesis of gastric mucosal lesions induced by indomethacin in rats. Digestion. 1991;49:175-84.
  • 47. Almasaudi SB, Abbas AT, Al-Hindi RR, El-Shitany NA, Abdel-Dayem UA, Ali SS, et al. Manuka honey exerts antioxidant and anti-inflammatory activities that promote healing of acetic acid-induced gastric ulcer in rats. Evidence-Based Complementary and Alternative Medicine. 2017;2017.
  • 48. da Silva LM, Allemand A, Mendes DAG, dos Santos AC, André E, de Souza LM, et al. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system. Food and chemical toxicology. 2013;51:179-87.
  • 49. Karakoyun B, Yüksel M, Ercan F, Erzik C, Yeğen BÇ. Alpha-lipoic acid improves acetic acid-induced gastric ulcer healing in rats. Inflammation. 2009;32:37-46.
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There are 62 citations in total.

Details

Primary Language Turkish
Subjects Medical Physiology
Journal Section Research
Authors

Sevil Arabacı Tamer 0000-0002-8701-6894

Alper Yıldırım This is me 0000-0002-3328-1692

Ozge Cevik 0000-0002-9325-3757

Burak Aksu This is me 0000-0002-3439-9158

Meral Yüksel 0000-0002-4760-3306

Ekin Kuntsal This is me 0000-0002-1330-9221

Serap Sirvancı 0000-0001-7683-4587

Berrak Yeğen 0000-0003-0791-0165

Publication Date March 31, 2021
Acceptance Date October 20, 2020
Published in Issue Year 2021 Volume: 46 Issue: 1

Cite

MLA Arabacı Tamer, Sevil et al. “Melatoninin bağırsak mikrobiyotasını düzenleyici Etkileri aracılığıyla sıçanlarda Asetik Asitle oluşturulmuş Mide ülserinde Hafifletici Etkileri”. Cukurova Medical Journal, vol. 46, no. 1, 2021, pp. 186-00.