title: Mechanistic insight into beta-carotene-mediated protection against ulcerative colitis-associated local and systemic damage in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  β-CAR ameliorated UC-associated local and systemic damage in mice by acting on multiple targets.
authors: 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, priyankatrvd2@gmail.com.
authors: P P
authors: PP
authors: Trivedi
authors: G B
authors: GB
authors: Jena
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D020552:Comet Assay; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019207:beta Carotene / Q000097:blood / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C526318:CCN2 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D062793:Occludin; C568986:Ocln protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D062725:Tight Junction Proteins; D014409:Tumor Necrosis Factor-alpha; D019207:beta Carotene; D055513:Connective Tissue Growth Factor; D016264:Dextran Sulfate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D005978:Glutathione