Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5851051 | Food and Chemical Toxicology | 2013 | 17 Pages |
Abstract
Ulcerative colitis affects many people worldwide. Inflammation and oxidative stress play a vital role in its pathogenesis. Previously, we reported that ulcerative colitis leads to systemic genotoxicity in mice. The present study was aimed at elucidating the role of α-lipoic acid in ulcerative colitis-associated local and systemic damage in mice. Experimental colitis was induced using 3%w/v dextran sulfate sodium in drinking water for 2 cycles. α-Lipoic acid was administered in a co-treatment (20, 40, 80 mg/kg bw) and post-treatment (80 mg/kg bw) schedule. Various biochemical parameters, histological evaluation, comet and micronucleus assays, immunohistochemistry and western blot analysis were employed to evaluate the effect of α-lipoic acid in mice with ulcerative colitis. The protective effect of α-lipoic acid was mediated through the modulation of nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, NADPH: quinone oxidoreductase-1, matrix metalloproteinase-9 and connective tissue growth factor. Further, ulcerative colitis led to an increased gut permeability, plasma lipopolysaccharide level, systemic inflammation and genotoxicity in mice, which was reduced with α-lipoic acid treatment. The present study identifies the underlying mechanisms involved in α-lipoic acid-mediated protection against ulcerative colitis and the associated systemic damage in mice.
Keywords
NF-κBTBARSSTAT3MMP-9CTGFHBSSCOX-2GSHNrf2NMPADSSDAILPSNQO-1FPGDABVCAM-1OTMLMPAMPODMSOH&EEDTAα-Lipoic acidethylenediamine tetraacetic acidinflammationinterleukinOxidative stresstumor necrosis factor-alphatail momentdimethylsulphoxideGenotoxicityDextran sulfate sodiumCyclooxygenase-2disease activity indextail lengthnuclear erythroid 2-related factor 2Connective tissue growth factorTNF-αNuclear factor-kappa Bformamidopyrimidine DNA glycosylaseOlive tail momentlipopolysaccharideMatrix metalloproteinase-9signal transducer and activator of transcription 3Hank’s balanced salt solutionthiobarbituric acid-reactive substancesmyeloperoxidasenormal melting point agaroselow melting point agaroseHematoxylin and EosinVascular cell adhesion protein-1reduced glutathioneUlcerative colitis
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Authors
P.P. Trivedi, G.B. Jena,