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Erschienen in:
01.06.2015 | Original Contribution
Mechanistic insight into beta-carotene-mediated protection against ulcerative colitis-associated local and systemic damage in mice
Erschienen in: European Journal of Nutrition | Ausgabe 4/2015
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Purpose
Ulcerative colitis (UC), a chronic gastrointestinal disorder, is a debilitating disease affecting many people across the globe. Research suggests that the levels of several antioxidants, including β-carotene (β-CAR), decrease in the serum of patients with UC. The present study was aimed at elucidating the molecular mechanisms involved in β-CAR-mediated protection against UC in mice.
Methods
UC was induced in mice using 3 %w/v dextran sulfate sodium in drinking water for two cycles; one cycle comprised of 7 days of dextran sulfate sodium-treated water followed by 14 days of normal drinking water. β-CAR was administered at the doses of 5, 10 and 20 mg/kg bw/day, po throughout the experiment. The effect of β-CAR in mice with UC was evaluated using biochemical parameters, histological evaluation, comet and micronucleus assays, immunohistochemistry and Western blot analysis.
Results
The results indicated that β-CAR treatment ameliorated the severity of UC by modulating various molecular targets such as 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, β-CAR treatment maintained the gut integrity by increasing the expression of a tight junction protein, occludin, which was decreased in the colon of mice with UC. Also β-CAR treatment significantly reduced UC-associated elevated plasma lipopolysaccharide level, systemic inflammation and genotoxicity.
Conclusion
β-CAR ameliorated UC-associated local and systemic damage in mice by acting on multiple targets.