Laura E Ewing1,2, Isabelle R Miousse1,3, Rupak Pathak4, Charles M Skinner1, Stanley Kosanke5, Marjan Boerma4, Martin Hauer-Jensen4, Igor Koturbash1. 1. Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A. 2. Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A. 3. Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A. 4. Division of Radiation Health, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A. 5. Heartland Veterinary Pathology Services, PLLC, Oklahoma City, Oklahoma City, OK, U.S.A.
Abstract
Purpose: Growing rates of metabolic syndrome and associated obesity warrant the development of appropriate animal models for better understanding of how those conditions may affect sensitivity to IR exposure.Materials and methods: We subjected male NZO/HlLtJ mice, a strain prone to spontaneous obesity and diabetes, to 0, 5.5, 6.37, 7.4 or 8.5 Gy (137Cs) of total body irradiation (TBI). Mice were monitored for 30 days, after which proximal jejunum and colon tissues were collected for further histological and molecular analysis. Results: Obese NZO/HlLtJ male mice are characterized by their lower sensitivity to IR at doses of 6.37 Gy and under, compared to other strains. Further escalation of the dose, however, results in a steep survival curve, reaching LD100/30 values at a dose of 8.5 Gy. Alterations in the expression of various tight junction-related proteins coupled with activation of inflammatory responses and cell death were the main contributors to the gastrointestinal syndrome.Conclusions: We demonstrate that metabolic syndrome with exhibited hyperglycemia but without alterations to the microvasculature is not a pre-requisite of the increased sensitivity to TBI at high doses. Our studies indicate the potential of NZO/HlLtJ mice for the studies on the role of metabolic syndrome in acute radiation toxicity.
Purpose: Growing rates of metabolic syndrome and associated obesity warrant the development of appropriate animal models for better understanding of how those conditions may affect sensitivity to IR exposure.Materials and methods: We subjected male NZO/HlLtJ mice, a strain prone to spontaneous obesity and diabetes, to 0, 5.5, 6.37, 7.4 or 8.5 Gy (137Cs) of total body irradiation (TBI). Mice were monitored for 30 days, after which proximal jejunum and colon tissues were collected for further histological and molecular analysis. Results:Obese NZO/HlLtJ male mice are characterized by their lower sensitivity to IR at doses of 6.37 Gy and under, compared to other strains. Further escalation of the dose, however, results in a steep survival curve, reaching LD100/30 values at a dose of 8.5 Gy. Alterations in the expression of various tight junction-related proteins coupled with activation of inflammatory responses and cell death were the main contributors to the gastrointestinal syndrome.Conclusions: We demonstrate that metabolic syndrome with exhibited hyperglycemia but without alterations to the microvasculature is not a pre-requisite of the increased sensitivity to TBI at high doses. Our studies indicate the potential of NZO/HlLtJ mice for the studies on the role of metabolic syndrome in acute radiation toxicity.
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Authors: Dror S Shouval; Amlan Biswas; Yu Hui Kang; Alexandra E Griffith; Liza Konnikova; Ivan D Mascanfroni; Naresh S Redhu; Sandra M Frei; Michael Field; Andria L Doty; Jeffrey D Goldsmith; Atul K Bhan; Anthony Loizides; Batia Weiss; Baruch Yerushalmi; Tadahiro Yanagi; Xiuli Lui; Francisco J Quintana; Aleixo M Muise; Christoph Klein; Bruce H Horwitz; Sarah C Glover; Athos Bousvaros; Scott B Snapper Journal: Gastroenterology Date: 2016-09-28 Impact factor: 22.682
Authors: Charles M Skinner; Intawat Nookaew; Laura E Ewing; Thidathip Wongsurawat; Piroon Jenjaroenpun; Charles M Quick; Eric U Yee; Brian D Piccolo; Mahmoud ElSohly; Larry A Walker; Bill Gurley; Igor Koturbash Journal: J Diet Suppl Date: 2020-05-13