期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 59, 期 -, 页码 339-355出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2013.06.019
关键词
Ulcerative colitis; Inflammation; Oxidative stress; Genotoxicity; alpha-Lipoic acid
资金
- National Institute of Pharmaceutical Education and Research (NIPER), Mohali
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 alpha-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. alpha-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 alpha-lipoic acid in mice with ulcerative colitis. The protective effect of alpha-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 alpha-lipoic acid treatment. The present study identifies the underlying mechanisms involved in alpha-lipoic acid-mediated protection against ulcerative colitis and the associated systemic damage in mice. (c) 2013 Elsevier Ltd. All rights reserved.
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