title: Melatonin reduces ulcerative colitis-associated local and systemic damage in mice: investigation on possible mechanisms.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Melatonin ameliorated ulcerative colitis-associated local and systemic damage in mice.
authors: 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.
authors: P P
authors: PP
authors: Trivedi
authors: G B
authors: GB
authors: Jena
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D062793:Occludin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011897:Random Allocation; D012720:Severity of Illness Index
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D008070:Lipopolysaccharides; D062793:Occludin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin
references: Mediators Inflamm. 2005 Aug 31;2005(4):185-93
references: 16192667
references: Int J Dent. 2012;2012:720185
references: 22899929
references: J Pineal Res. 2007 Apr;42(4):364-70
references: 17439553
references: Ter Arkh. 2010;82(12):64-8
references: 21516743
references: J Pineal Res. 2009 Aug;47(1):43-55
references: 19522738
references: Free Radic Biol Med. 2009 Nov 1;47(9):1304-9
references: 19666107
references: J Physiol Pharmacol. 2011 Jun;62(3):327-34
references: 21893693
references: Cell Biol Int. 1996 Oct;20(10):687-92
references: 8969462
references: Eur J Pharmacol. 2011 Sep 30;667(1-3):419-24
references: 21693115
references: Gut. 2007 Jun;56(6):847-54
references: 17229795
references: Curr Opin Investig Drugs. 2006 May;7(5):423-31
references: 16729718
references: J Neurochem. 2010 Sep;114(6):1687-700
references: 20584104
references: Cancer Res. 2009 Jun 1;69(11):4827-34
references: 19487293
references: J Gastroenterol. 2010 Jun;45(6):571-83
references: 20213337
references: Gastroenterol Hepatol (N Y). 2012 Jan;8(1):29-38
references: 22347830
references: J Ethnopharmacol. 2013 Apr 19;146(3):750-9
references: 23395625
references: Indian J Gastroenterol. 2012 Dec;31(6):299-306
references: 23073755
references: J Pineal Res. 2011 Aug;51(1):44-60
references: 21752096
references: Dig Dis Sci. 2006 Sep;51(9):1538-45
references: 16927145
references: Toxicology. 2002 Mar 20;172(2):143-8
references: 11882353
references: J Pineal Res. 2010 May;48(4):324-31
references: 20433640
references: J Pineal Res. 2011 Apr;50(3):328-35
references: 21244479
references: J Pineal Res. 2010 Oct;49(3):312-20
references: 20738757
references: Eur J Pharmacol. 2003 May 23;469(1-3):145-52
references: 12782196
references: PLoS One. 2012;7(9):e38801
references: 22962574
references: Chem Biol Interact. 2013 Jan 25;201(1-3):19-30
references: 23261717
references: Mutat Res. 1996 Jul 10;369(1-2):1-6
references: 8700174
references: J Pineal Res. 1995 Aug;19(1):31-9
references: 8609593
references: Chem Biol Interact. 2009 Jan 27;177(2):128-36
references: 19028472
references: Eur J Pharmacol. 2007 Oct 1;571(2-3):116-9
references: 17720153
references: Dig Dis Sci. 2011 Mar;56(3):715-20
references: 20676767
references: Mutagenesis. 2012 Jan;27(1):77-86
references: 21980144
references: Acta Pharmacol Sin. 2002 Oct;23(10):882-6
references: 12370092
references: J Pineal Res. 2001 Jan;30(1):1-12
references: 11168901
references: Dig Dis Sci. 2002 Oct;47(10):2336-48
references: 12395907
references: J Pineal Res. 2011 Aug;51(1):1-16
references: 21752095
references: J Pineal Res. 2003 Jan;34(1):75-8
references: 12485375
references: Mutat Res. 2012 May 15;744(2):172-83
references: 22414559
references: Postgrad Med J. 2005 Oct;81(960):667-72
references: 16210467
references: Mutat Res. 2008 May 31;653(1-2):134-9
references: 18468946
references: Exp Biol Med (Maywood). 2012 Jun;237(6):670-7
references: 22728708
references: J Pineal Res. 2006 Nov;41(4):363-73
references: 17014694
references: Anal Biochem. 1979 Jun;95(2):351-8
references: 36810
references: Nat Rev Immunol. 2004 Aug;4(8):617-29
references: 15286728
references: Fundam Clin Pharmacol. 2013 Jun;27(3):299-307
references: 22151426
references: Free Radic Res. 2012 Nov;46(11):1339-45
references: 22856328
references: Mutat Res. 2010 Aug 7;690(1-2):12-23
references: 19799917
references: World J Gastroenterol. 2003 Jun;9(6):1307-11
references: 12800246
references: Gastroenterology. 1989 Aug;97(2):326-37
references: 2545504
references: Curr Top Med Chem. 2002 Feb;2(2):181-97
references: 11899100
references: J Pineal Res. 2007 Aug;43(1):56-64
references: 17614836
references: World J Gastroenterol. 2008 Feb 14;14(6):918-24
references: 18240350
references: Eur J Pharmacol. 1998 Dec 11;363(1):57-63
references: 9877082
references: Chem Biol Interact. 2010 Jan 5;183(1):85-97
references: 19900424
references: J Pharm Pharmacol. 2001 Oct;53(10):1393-401
references: 11697548
references: Carcinogenesis. 1993 Sep;14(9):1733-5
references: 8403192
references: Biochem Mol Biol Int. 1995 Dec;37(6):1063-70
references: 8747536
references: J Pineal Res. 2008 Sep;45(2):166-73
references: 18429971
references: Toxicology. 2009 Feb 4;256(1-2):75-82
references: 19061934
references: Mutat Res. 1997 Jun 13;391(1-2):87-9
references: 9219552
references: Gastroenterology. 1991 May;100(5 Pt 1):1180-6
references: 2013367
references: Methods Mol Biol. 1999;113:203-12
references: 10443422
references: Eur J Pharmacol. 2010 Oct 10;644(1-3):160-8
references: 20624385
references: Toxicology. 1999 Nov 29;139(1-2):81-91
references: 10614689
references: J Pineal Res. 2011 Oct;51(3):286-96
references: 21545523
references: J Pineal Res. 2010 Oct;49(3):271-82
references: 20626588
references: Science. 2012 Oct 5;338(6103):120-3
references: 22903521
references: J Pineal Res. 2008 Jan;44(1):45-51
references: 18078447
references: Endocrine. 2005 Jul;27(2):189-200
references: 16217132
references: Saudi Med J. 2008 Aug;29(8):1088-94
references: 18690297
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713
references: Inflamm Bowel Dis. 2012 Aug;18(8):1399-410
references: 22223479
references: J Pineal Res. 1999 Nov;27(4):202-9
references: 10551767
references: J Hepatol. 2011 Dec;55(6):1391-9
references: 21703208
references: Biochim Biophys Acta. 1979 Jan 4;582(1):67-78
references: 760819