title: Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice.
abstract: Melatonin is known as a strong antioxidant and possesses anti-inflammatory properties. Recently, melatonin was shown to improve colitis in animal models of inflammatory bowel diseases. The aim of the present study was to characterize the role of melatonin receptors (MT) in the anti-inflammatory effect of melatonin and to assess the anti-inflammatory potential of two novel MT receptor agonists, Neu-P11 and Neu-P67, in the mouse model of trinitrobenzenesulfonic acid (TNBS)-induced colitis. Colitis was induced on day 1 by intracolonic (i.c.) administration of TNBS in 30 % ethanol in saline. Melatonin (4 mg/kg, per os (p.o.)), Neu-P11 (20 mg/kg, p.o.; 50 mg/kg, intraperitoneally (i.p.), 50 mg/kg, i.c.), and Neu-P67 (20 mg/kg, p.o.) were given twice daily for 3 days. Luzindole (5 mg/kg, i.p.) was injected 15 min prior to melatonin administration. On day 4, macroscopic and microscopic damage scores were assessed and myeloperoxidase (MPO) activity quantified using O-dianisidine-based assay. Melatonin significantly attenuated colitis in mice, as indicated by the macroscopic score (1.90 ± 0.34 vs. 3.82 ± 0.62 for melatonin- and TNBS-treated mice, respectively), ulcer score (0.87 ± 0.18 vs. 1.31 ± 0.19, respectively), and MPO activity (4.68 ± 0.70 vs.6.26 ± 0.94, respectively). Luzindole, a MT receptor antagonist, did not inhibit the anti-inflammatory effect of melatonin (macroscopic score 1.12 ± 0.22, ulcer score 0.50 ± 0.16); however, luzindole increased MPO activity (7.57 ± 1.05). MT receptor agonists Neu-P11 and Neu-P67 did not improve inflammation induced by TNBS. Melatonin, but not MT receptor agonists, exerts potent anti-inflammatory action in acute TNBS-induced colitis. Our data suggests that melatonin attenuates colitis by additional, MT receptor-independent pathways.
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Zielińska
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Jarmuż
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Sałaga
authors.affiliation: Department of Pathology, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Radzisław
authors.initials: R
authors.lastname: Kordek
authors.affiliation: Neurim Pharmaceuticals LTD, Tel-Aviv, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Laudon
authors.affiliation: Walter Brendel Center of Experimental Medicine, University of Munich, Munich, Germany.|Department of Medicine, Division of Gastroenterology, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Storr
authors.affiliation: Department of Biochemistry, Medical University of Lodz, Lodz, Poland. jakub.fichna@umed.lodz.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D011714:Pyrans / Q000627:therapeutic use; D044094:Receptors, Melatonin / Q000819:agonists; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D007211:Indoles; D011714:Pyrans; D044094:Receptors, Melatonin; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D008550:Melatonin; C581609:N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide
keywords: Colitis; Inflammatory bowel diseases; Melatonin; Melatonin receptor agonists