Melatonin's role as a co-adjuvant treatment in colonic diseases: A review

• Published in: Life sciences (1973) Vol. 170; pp. 72 - 81
• Main Authors: Esteban-Zubero, Eduardo, López-Pingarrón, Laura, Alatorre-Jiménez, Moisés Alejandro, Ochoa-Moneo, Purificación, Buisac-Ramón, Celia, Rivas-Jiménez, Miguel, Castán-Ruiz, Silvia, Antoñanzas-Lombarte, Ángel, Tan, Dun-Xian, García, José Joaquín, Reiter, Russel J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-02-2017; Elsevier BV
• Subjects: Adjuvant therapy; Animals; Antioxidants; Cell Proliferation; Cholecystokinin; Circadian rhythms; Colitis - metabolism; Colitis, Ulcerative - metabolism; Colonic Diseases - metabolism; Constipation; Crohn's Disease; Crohns disease; Diarrhea; Digestive system; Diseases; Enterocolitis; Enterocolitis, Necrotizing - metabolism; Enzymes; Food intake; Gastric motility; Gastrointestinal diseases; Gastrointestinal Diseases - metabolism; Gastrointestinal Diseases - therapy; Gastrointestinal tract; Gastrointestinal Tract - metabolism; Gene expression; Humans; Immune response; Immune system; Inflammatory bowel disease; Innate immunity; Intestinal transit time; Intestine; Intestines - metabolism; Irritable bowel syndrome; Irritable Bowel Syndrome - metabolism; Melatonin; Melatonin - physiology; Melatonin - secretion; Melatonin receptors; Mucosa; Necrotizing enterocolitis; Organs; Oxidative stress; Pineal gland; Pineal Gland - metabolism; Receptors; Receptors, Melatonin - metabolism; Resists; Risk Factors; Serotonin; Serotonin - metabolism; Sleep; Th17 Cells - cytology; Th2 Cells - cytology; Transit time; Ulcerative colitis; Melatonin; Necrotizing enterocolitis; HO-1; LPO; MDA; HIOMT; MPO; UC; NF-κB; 6-OHMs; Nrf2; RNS; GRd; iNOS; IBS; GSH; EC; CD; CACC; NQO-1; PGE2; IL; SOD; MT2; Crohn's disease; GPx; MMP; IBS-D; IBS-C; GIT; NOS; TNF-α; PTX-3; MEL; CRF; Gastrointestinal diseases; CAT; Irritable bowel syndrome; CCK2; Keap1; 5-HT; HCY; Ulcerative colitis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2016.11.031

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.
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