Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: Studies on inflammation, oxidative stress, DNA damage and fibrosis
•α-Lipoic acid (LA) protected against ulcerative colitis (UC) in mice.•LA reduced inflammation, oxidative stress, DNA damage and fibrosis in mice with UC.•It prevented UC-induced increased gut permeability and reduced plasma LPS level.•It further reduced systemic inflammation and genotoxicity in mic...
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Published in | Food and chemical toxicology Vol. 59; pp. 339 - 355 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.09.2013
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | •α-Lipoic acid (LA) protected against ulcerative colitis (UC) in mice.•LA reduced inflammation, oxidative stress, DNA damage and fibrosis in mice with UC.•It prevented UC-induced increased gut permeability and reduced plasma LPS level.•It further reduced systemic inflammation and genotoxicity in mice with UC.•It ameliorated UC-induced local as well as systemic damage in mice.
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, 80mg/kg bw) and post-treatment (80mg/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. |
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Bibliography: | http://dx.doi.org/10.1016/j.fct.2013.06.019 |
ISSN: | 0278-6915 1873-6351 |
DOI: | 10.1016/j.fct.2013.06.019 |