The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease

Tharwat S Kandil, Amany A Mousa, Ahmed A El-Gendy, Amr M Abbas, Tharwat S Kandil, Amany A Mousa, Ahmed A El-Gendy, Amr M Abbas

Abstract

Background: Gastro-Esophageal Reflux Disease (GERD) defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many drugs are used for the treatment of GERD such as omeprazole (a proton pump inhibitor) which is a widely used antiulcer drug demonstrated to protect against esophageal mucosal injury. Melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models. The aim of this study is to evaluate the role of exogenous melatonin in the treatment of reflux disease in humans either alone or in combination with omeprazole therapy.

Methods: 36 persons were divided into 4 groups (control subjects, patients with reflux disease treated with melatonin alone, omeprazole alone and a combination of melatonin and omeprazole for 4 and 8 weeks) Each group consisted of 9 persons. Persons were subjected to thorough history taking, clinical examination, and investigations including laboratory, endoscopic, record of esophageal motility, pH-metry, basal acid output and serum gastrin.

Results: Melatonin has a role in the improvement of Gastro-esophageal reflux disease when used alone or in combination with omeprazole. Meanwhile, omeprazole alone is better used in the treatment of GERD than melatonin alone.

Conclusion: The present study showed that oral melatonin is a promising therapeutic agent for the treatment of GERD. It is an effective line of treatment in relieving epigastric pain and heartburn. However, further studies are required to confirm the efficacy and long-term safety of melatonin before being recommended for routine clinical use.

Trial registration: QA13NCT00915616.

References

    1. Vakil N, VanZanten S, Dent J, Kahrilas P, Jones R. The definition of GERD: A global evidence-based consensus. Gastroenterology. 2005. pp. 130A–394. [#M2010]
    1. Locke GR, Talley NJ, Fett SL. et al.Prevalence and clinical spectrum of gastroesophageal reflux:a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997;112:1448–56. doi: 10.1016/S0016-5085(97)70025-8.
    1. Messner M, Huether G, Lorf T, Ramadori G, Schworer H. Presence of melatonin in the human hepatobiliary - gastrointestinal tract. Life Sci. 2001;69:543–551. doi: 10.1016/S0024-3205(01)01143-2.
    1. Motilva V, Cabeza J, Alarcon de la Lastra C. New issues about melatonin and its effects on the digestive system. Curre Pharm Des. 2001;7:909–931. doi: 10.2174/1381612013397681.
    1. Huether G. The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates. Experientia. 1993;49:665–670. doi: 10.1007/BF01923948.
    1. Bilici D, Suleyman H, Banoglu ZN. Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its antioxidant effect. Dig Dis Sci. 2003;47:856–861. doi: 10.1023/A:1014764705864.
    1. Kato K, Murai I, Asai S, Komuro S, Matsuno Y, Matsukawa Y, Kurosaka H, Iwasaki A, Ishikawa K, Arakawa Y. Central effect of melatonin against stress-induced gastric ulcers in rats. Neuroreport. 1997;8(9-10):2305–9.
    1. Middleton B. In: Methods in molecular biology, Hormone assays in biological fluids. wheeler MS, Hutchinson JS, editor. Humana press, Surrey, UK; 2006. Measurement of melatonin and 6 sulphatoxymelatonin; pp. 235–254. full_text.
    1. Gad El-Hak N, Abo Zied M, Aboelenen A, Fouad A, Abd Alla T, El-Shoubary M, Kandel T, Hamdy E, Abdel Wahab M, Fathy O, El-ebidy G, Sultan A, Elfiky A, Elghwalby N, Ezzat F. Short gastric vessels division in laparoscopic Nissen Fundoplication. Hepatogastro-enterology. 2005;52(66):1742–1747.
    1. Paget GE, Barnes JM. In: Evaluation of drug activities:Pharmacometrics. Lawrences DR, Bacharach AL, editor. New York: Academic press; 1964. Toxicity studies; pp. 1–155.
    1. Neville D, Yeomans MD, Razc I, john M, Van CJ. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. The new England Journal of Medicine. 2006;338(11):719–726.
    1. Armitage P, Berry G. Statistical Methods in Medical Research. 3. Blackwell Scientific Publications, London; 1994. Statistical methods in medical research; pp. 292–305.
    1. Reiter RJ. Pineal melatonin: Cell biology of its synthesis and physiological interactions. Endocrinol Rev. 1974;12:151–180. doi: 10.1210/edrv-12-2-151.
    1. Zhdanova IV, Wurtman RJ, Lynch HJ. Sleep-inducing effect of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995;57:552–558. doi: 10.1016/0009-9236(95)90040-3.
    1. Reiter RJ. Melatonin: Lowering the high price of free radicals. News Physiol Sci. 2000;15:246–250.
    1. Konturek SJ, Konturek PC, Brzozowska T, Bubenik GA. Role of melatonin in upper gastrointestinal tract. Journal of physiology and pharmacology. 2007;58(supp 6):23–52.
    1. Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon M, Bandyopadhyay D. Neurally-mediated and neurally-independent beneficial actions of melatonin in the gastrointestinal tract. J Physiol Pharmacol. 2003;54(4):113–25.
    1. Klupiñska G, Niewska wi.-Jarosiñska1 M, Harasiuk1 A, Chojnacki1 C. Nocturnal secretion of melatonin in patients with upper digestive tract disorders. Journal of physiology and pharmacology. 2006;57(Supp5):41–50.
    1. Bubenik GA, Ayles HL, Friendship RM, Brown GM, Ball RO. Relationship between melatonin levels in plasma and gastrointestinal tissues and the incidence and severity of gastric ulcers in pigs. J Pineal Res. 1998;24:62–66. doi: 10.1111/j.1600-079X.1998.tb00367.x.
    1. Otsuka M, Kato K, Ichiro M, Satoshi A, Iwasaki A, Arakawa Y. Roles of nocturnal melatonin and the pineal gland in modulation of water immersion restraint stress-induced gastric mucosa lesions in rats. J Pineal Res. 2001;30:82–86. doi: 10.1034/j.1600-079X.2001.300203.x.
    1. Karasek M, Winczyk K. Melatonin in humans. J Physiol Pharmacol. 2006. pp. 19–39.
    1. Domingues-Rodriguez A, Abreu-Gonzalez P, Garcia M. Light/dark patterns of interleukin-6 in relation to the pineal hormone melatonin in patients with acute myocardial infarction. Cytokine. 2004;26(2):89–93. doi: 10.1016/j.cyto.2004.01.003. 49.
    1. Bandyopadhyay D, Chattopadhyay A. Reactive oxygen species-induced gastric ulceration: Protection by melatonin. Current Medicinal Chemistry. 2006;13:1187–1202. doi: 10.2174/092986706776360842.
    1. Werbach MR. Melatonin for the treatment of gastroesophageal reflux disease. Altern Ther Health Med. 2008;14(4):54–8.
    1. Gavert G, Harvey DL. Undesirable inflammatory responses. McGraw-Hill, London; 1995. Normal inflammatory responses to injury. Normal inflammatory responses to microorganism.
    1. Pereira RS. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J Pineal Res. 2006;41:195–200. doi: 10.1111/j.1600-079X.2006.00359.x.
    1. Konturek SJ, Zayachkivska O, Havryluk XO. Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves. J physiology and pharmacology. 2007;58(2):361–77.
    1. Sener-Muratoglu G, Paskaloglu K, Arbak S, Hurdag C, Ayanoglu-Dulger G. Protective effect of famotidine, omeprazole, and melatonin against acetylsalicylic acid-induced gastric damage in rats. Dig Dis Sci. 2001;46(2):318–30. doi: 10.1023/A:1005652815921.
    1. Konturek SJ, Konturek PC, Brzozowska I, Pawlik M, Sliwowski Z, Czenikiewicz-Guzik M, Kwiecieñ S, Brzozowski T, Bubenik GA, Pawlik WW. Localization and biological activities of melatonin in intact and diseased gastrointestinal tract (git) Journal of physiology and pharmacology. 2007;58(3):381–405.
    1. Bandyopadhyay D, Bandyopadhyay A, Das PK, Reiter RJ. Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage. J Pineal Res. 2002;33(1):1–7. doi: 10.1034/j.1600-079X.2002.01107.x.
    1. Reiter R J, Tan DX, Manchester LC. In: Handbook of Antioxidants. 2. Cadenas E, Packer L, editor. Marcel Dekker, New York; 2002. Antioxidative capacity of melatonin; pp. 565–613.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다