Melatonin Reduces Ulcerative Colitis-Associated Local and Systemic Damage in Mice: Investigation on Possible Mechanisms

• Published in: Digestive diseases and sciences 2013-12, Vol.58 (12), p.3460-3474
• Main Authors: Trivedi, P. P., Jena, G. B.
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biochemistry; Biomarkers - metabolism; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Colon - drug effects; Colon - metabolism; Colon - pathology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Dextran; DNA Damage - drug effects; Gastroenterology; Hepatology; Immunohistochemistry; Inflammation; Investigations; Lipopolysaccharides - blood; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Mice; Occludin - metabolism; Oncology; Original Article; Oxidative Stress - drug effects; Permeability; Permeability - drug effects; Random Allocation; Severity of Illness Index; Sulfates; Transplant Surgery; Ulcerative colitis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-013-2831-6

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.