P P Trivedi1, G B Jena. 1. 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.
Abstract
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.
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.
Authors: Anat Ben-Dor; Michael Steiner; Larisa Gheber; Michael Danilenko; Noga Dubi; Karin Linnewiel; Anat Zick; Yoav Sharoni; Joseph Levy Journal: Mol Cancer Ther Date: 2005-01 Impact factor: 6.261
Authors: Vladimíra Muzáková; Roman Kand'ár; Milan Meloun; Jirí Skalický; Karel Královec; Pavla Záková; Petr Vojtísek Journal: Int J Vitam Nutr Res Date: 2010-12 Impact factor: 1.784
Authors: Elena Talero; Sofía García-Mauriño; Javier Ávila-Román; Azahara Rodríguez-Luna; Antonio Alcaide; Virginia Motilva Journal: Mar Drugs Date: 2015-09-30 Impact factor: 5.118
Authors: Javier Ávila-Román; Sara García-Gil; Azahara Rodríguez-Luna; Virginia Motilva; Elena Talero Journal: Mar Drugs Date: 2021-09-23 Impact factor: 5.118
Authors: Martje N Erkelens; Gera Goverse; Tanja Konijn; Rosalie Molenaar; Marieke R Beijer; Jan Van den Bossche; Kyra E de Goede; Sanne G S Verberk; Wouter J de Jonge; Joke M M den Haan; Reina E Mebius Journal: Front Immunol Date: 2020-03-31 Impact factor: 7.561