title: Melatonin's role as a co-adjuvant treatment in colonic diseases: A review.
abstract: Melatonin is produced in the pineal gland as well as many other organs, including the enterochromaffin cells of the digestive mucosa. Melatonin is a powerful antioxidant that resists oxidative stress due to its capacity to directly scavenge reactive species, to modulate the antioxidant defense system by increasing the activities of antioxidant enzymes, and to stimulate the innate immune response through its direct and indirect actions. In addition, the dysregulation of the circadian system is observed to be related with alterations in colonic motility and cell disruptions due to the modifications of clock genes expression. In the gastrointestinal tract, the activities of melatonin are mediated by melatonin receptors (MT2), serotonin (5-HT), and cholecystokinin B (CCK2) receptors and via receptor-independent processes. The levels of melatonin in the gastrointestinal tract exceed by 10-100 times the blood concentrations. Also, there is an estimated 400 times more melatonin in the gut than in the pineal gland. Gut melatonin secretion is suggested to be influenced by the food intake. Low dose melatonin treatment accelerates intestinal transit time whereas high doses may decrease gut motility. Melatonin has been studied as a co-adjuvant treatment in several gastrointestinal diseases including irritable bowel syndrome (IBS), constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. The purpose of this review is to provide information regarding the potential benefits of melatonin as a co-adjuvant treatment in gastrointestinal diseases, especially IBS, Crohn's disease, ulcerative colitis, and necrotizing enterocolitis.
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain. Electronic address: eezubero@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Esteban-Zubero
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: López-Pingarrón
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Moisés Alejandro
authors.initials: MA
authors.lastname: Alatorre-Jiménez
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Ochoa-Moneo
authors.affiliation: Primary Care Unit, Sector Zaragoza III, Avenida San Juan Bosco 5, 50009 Zaragoza, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Buisac-Ramón
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivas-Jiménez
authors.affiliation: Primary Care Unit, Sector Zaragoza III, Avenida San Juan Bosco 5, 50009 Zaragoza, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castán-Ruiz
authors.affiliation: Department of Medicine, Psychiatry and Dermatology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Antoñanzas-Lombarte
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Dun-Xian
authors.initials: DX
authors.lastname: Tan
authors.affiliation: Department of Pharmacology and Physiology, University of Zaragoza. Calle Domingo Miral s/n, 50009 Zaragoza, Spain.
authors.forename: José Joaquín
authors.initials: JJ
authors.lastname: García
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: reiter@uthscsa.edu.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003092:Colitis / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism; D003108:Colonic Diseases / Q000378:metabolism*; D020345:Enterocolitis, Necrotizing / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000378:metabolism* / Q000628:therapy; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism* / Q000502:physiology*; D010870:Pineal Gland / Q000378:metabolism; D044094:Receptors, Melatonin / Q000378:metabolism; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism; D012890:Sleep; D058504:Th17 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
chemical_list: D044094:Receptors, Melatonin; D012701:Serotonin; D008550:Melatonin
keywords: Crohn's disease; Gastrointestinal diseases; Irritable bowel syndrome; Melatonin; Necrotizing enterocolitis; Ulcerative colitis