ORIGINAL CONTRIBUTION Mechanistic insight into beta-carotene-mediated protection against ulcerative colitis-associated local and systemic damage in mice P. P. Trivedi • G. B. Jena Received: 26 February 2014 / Accepted: 17 July 2014 Ó Springer-Verlag Berlin Heidelberg 2014 Abstract Purpose Ulcerative colitis (UC), a chronic gastrointesti- nal disorder, is a debilitating disease affecting many people across the globe. Research suggests that the levels of sev- eral antioxidants, including b-carotene (b-CAR), decrease in the serum of patients with UC. The present study was aimed at elucidating the molecular mechanisms involved in b-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. b- CAR was administered at the doses of 5, 10 and 20 mg/ kg bw/day, po throughout the experiment. The effect of b- CAR in mice with UC was evaluated using biochemical parameters, histological evaluation, comet and micronu- cleus assays, immunohistochemistry and Western blot analysis. Results The results indicated that b-CAR treatment ameliorated the severity of UC by modulating various molecular targets such as nuclear factor-kappa B, cyclo- oxygenase-2, interleukin 17, signal transducer and activa- tor of transcription 3, nuclear erythroid 2-related factor 2, matrix metalloproteinase-9 and connective tissue growth factor. Further, b-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 b-CAR treatment significantly reduced UC-associated elevated plasma lipopolysaccharide level, systemic inflammation and genotoxicity. Conclusion b-CAR ameliorated UC-associated local and systemic damage in mice by acting on multiple targets. Keywords Ulcerative colitis Á Inflammation Á Oxidative stress Á Fibrosis Á DNA damage Á b-Carotene Abbreviations UC Ulcerative colitis b-CAR b-Carotene NF-jB Nuclear factor-kappa B IL Interleukin MMP Matrix metalloproteinase DSS Dextran sulfate sodium COX-2 Cyclooxygenase-2 STAT3 Signal transducer and activator of transcription 3 Nrf2 Nuclear erythroid 2-related factor 2 NQO-1 NADPH: quinone oxidoreductase-1 CTGF Connective tissue growth factor End-III Endonuclease-III FPG Formamidopyrimidine DNA glycosylase H&E Hematoxylin and eosin DMSO Dimethylsulfoxide NMPA Normal melting point agarose LMPA Low melting point agarose EDTA Ethylenediamine tetraacetic acid HBSS Hank’s balanced salt solution DAI Disease activity index MPO Myeloperoxidase TNF-a Tumor necrosis factor-alpha TBARS Thiobarbituric acid-reactive substances GSH Reduced glutathione P. P. Trivedi Á G. B. Jena (&) Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Mohali 160062, Punjab, India e-mail: gbjena@gmail.com; gbjena@niper.ac.in P. P. Trivedi e-mail: priyankatrvd2@gmail.com 123 Eur J Nutr DOI 10.1007/s00394-014-0745-5