P P Trivedi1, G B Jena. 1. Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab, 160062, India, priyankatrvd2@gmail.com.
Abstract
BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic gastrointestinal disorder. Substantial research reveals that melatonin has beneficial effects in ulcerative colitis both experimentally and clinically. We have previously reported that ulcerative colitis was associated with local and systemic damage in mice. The purpose of this study was to reveal the novel targets of melatonin in its protective mechanism against ulcerative colitis in mice. We also wished to determine whether or not melatonin protected against ulcerative colitis-induced systemic damage in mice. METHODS: Ulcerative colitis was induced in mice by use of 3% (w/v) dextran sulfate sodium for two cycles. One cycle comprised 7 days of DSS-treated water followed by 14 days of normal drinking water. Melatonin was administered at doses of 2, 4, or 8 mg/kg bw/day, po throughout. The effect of melatonin in mice with UC was evaluated by use of biochemical data, histological evaluation, comet and micronucleus assays, immunohistochemistry, and western blot analysis. RESULTS: The results indicated that melatonin treatment ameliorated the severity of ulcerative colitis by modulating a variety of molecular targets, for example nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, matrix metalloproteinase-9, and connective tissue growth factor. Further, ulcerative colitis increased gut permeability, plasma lipopolysaccharide level, systemic inflammation, and genotoxicity. Melatonin treatment led to mucosal healing and reduced ulcerative colitis-induced elevated gut permeability and reduced the plasma LPS level, systemic inflammation, and genotoxicity. CONCLUSION: Melatonin ameliorated ulcerative colitis-associated local and systemic damage in mice.
BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic gastrointestinal disorder. Substantial research reveals that melatonin has beneficial effects in ulcerative colitis both experimentally and clinically. We have previously reported that ulcerative colitis was associated with local and systemic damage in mice. The purpose of this study was to reveal the novel targets of melatonin in its protective mechanism against ulcerative colitis in mice. We also wished to determine whether or not melatonin protected against ulcerative colitis-induced systemic damage in mice. METHODS:Ulcerative colitis was induced in mice by use of 3% (w/v) dextran sulfate sodium for two cycles. One cycle comprised 7 days of DSS-treated water followed by 14 days of normal drinking water. Melatonin was administered at doses of 2, 4, or 8 mg/kg bw/day, po throughout. The effect of melatonin in mice with UC was evaluated by use of biochemical data, histological evaluation, comet and micronucleus assays, immunohistochemistry, and western blot analysis. RESULTS: The results indicated that melatonin treatment ameliorated the severity of ulcerative colitis by modulating a variety of molecular targets, for example nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, matrix metalloproteinase-9, and connective tissue growth factor. Further, ulcerative colitis increased gut permeability, plasma lipopolysaccharide level, systemic inflammation, and genotoxicity. Melatonin treatment led to mucosal healing and reduced ulcerative colitis-induced elevated gut permeability and reduced the plasma LPS level, systemic inflammation, and genotoxicity. CONCLUSION:Melatonin ameliorated ulcerative colitis-associated local and systemic damage in mice.
Authors: E Gitto; D X Tan; R J Reiter; M Karbownik; L C Manchester; S Cuzzocrea; F Fulia; I Barberi Journal: J Pharm Pharmacol Date: 2001-10 Impact factor: 3.765
Authors: Janelle C Arthur; Ernesto Perez-Chanona; Marcus Mühlbauer; Sarah Tomkovich; Joshua M Uronis; Ting-Jia Fan; Barry J Campbell; Turki Abujamel; Belgin Dogan; Arlin B Rogers; Jonathan M Rhodes; Alain Stintzi; Kenneth W Simpson; Jonathan J Hansen; Temitope O Keku; Anthony A Fodor; Christian Jobin Journal: Science Date: 2012-08-16 Impact factor: 47.728