title: Protective effect of melatonin on myenteric neuron damage in experimental colitis in rats.
abstract: Inflammation of the colon in patients with ulcerative colitis (UC) causes pain and altered motility, at least in part through the damage of the myenteric neurons (MNs). Thus, it is important to evaluate new drugs for UC treatment that could also protect myenteric neurons efficiently. As a well-known neural protective and anti-inflammatory agent, melatonin could protect neurons from damage through the activation of the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling pathway. Therefore, we investigated the potential protective effect of melatonin against MN damage during colitis induced by 2,4-dinitrobenzene sulfonic acid (DNBS) in rats. Colitis was induced by intracolonic (i.c.) instillation of DNBS and treated with melatonin at a dose of 2.5 mg/kg for 4 days. The damage of MN in the left colon was immunohistochemically evaluated in different groups. Ulcerations and inflammation in the colon were semiquantitatively observed. Myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected to evaluate the inflammatory and oxidative stress status. The protein and mRNA expressions of Nrf2 and heme oxygenase-1 (HO-1) in the colon were detected by Western blot and quantitative polymerase chain reaction (qPCR), respectively. Melatonin partially prevented the loss of MN and alleviated the inflammation and oxidative stress induced by DNBS. In addition, melatonin markedly increased the Nrf2 and HO-1 level in the colitis. These results indicate that melatonin protects MN from damage by reducing inflammation and oxidative stress, effects that are partly mediated by the Nrf2-ARE pathway.
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Boxin
authors.identifier: http://orcid.org/0000-0002-5871-1003
authors.initials: B
authors.lastname: Shang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D020011:Protective Agents; C045305:2,4-dinitrofluorobenzene sulfonic acid; D008315:Malondialdehyde; D004139:Dinitrofluorobenzene; D009195:Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D008550:Melatonin
keywords: inflammation; melatonin; myenteric neurons; nuclear factor erythroid 2-related factor 2; oxidative stress; ulcerative colitis