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Tytuł:
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Gliadin effect on the oxidative balance and DNA damage: An in-vitro, ex-vivo study.
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Autorzy:
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Monguzzi E; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
Marabini L; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy.
Elli L; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy. Electronic address: .
Vaira V; Division of Pathology, IRCCS Ca' Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
Ferrero S; Division of Pathology, IRCCS Ca' Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy.
Ferretti F; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
Branchi F; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
Gaudioso G; Division of Pathology, IRCCS Ca' Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy.
Scricciolo A; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy.
Lombardo V; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy.
Doneda L; Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy.
Roncoroni L; Gastroenterology and Endoscopy Unit - Center for Prevention and Diagnosis of Celiac Disease, IRCCS Ca's Granda Foundation 'Ospedale Maggiore Policlinico', Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy.
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Źródło:
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Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver [Dig Liver Dis] 2019 Jan; Vol. 51 (1), pp. 47-54. Date of Electronic Publication: 2018 Jul 03.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: 2003- : Amsterdam : Elsevier
Original Publication: Roma, Italy : Editrice gastroenterologica italiana, c2000-
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MeSH Terms:
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Celiac Disease/*metabolism
DNA Fragmentation/*drug effects
Gliadin/*pharmacology
Oxidative Stress/*drug effects
Apoptosis ; Blotting, Western ; Caco-2 Cells/drug effects ; Comet Assay ; Enterocytes/drug effects ; Female ; Humans ; Intestinal Mucosa/drug effects ; Male ; Middle Aged
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Contributed Indexing:
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Keywords: Apoptosis; DNA damage; Oxidative stress; PT gliadin
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Substance Nomenclature:
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9007-90-3 (Gliadin)
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Entry Date(s):
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Date Created: 20180730 Date Completed: 20190613 Latest Revision: 20190613
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Update Code:
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20221216
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DOI:
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10.1016/j.dld.2018.06.020
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PMID:
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30055963
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Background: Gliadins are involved in gluten-related disorders and are responsible for the alteration of the cellular redox balance. It is not clear if the gliadin-related oxidative stress can induce DNA damage in enterocytes.
Aim: To investigate any possible genotoxicity caused by gliadin and to assess its relationship with oxidative stress in vitro and ex vivo.
Methods: Caco-2 cells were exposed for 6-12-24 h to increasing concentrations (250 μg/mL-1000 μg/mL) of digested gliadin. We investigated: cytotoxicity, oxidative balance (reactive oxygen species, ROS), DNA damage (comet assay and γ-H2AX detection), transglutaminase type 2 (TG2) activity and annexin V expression. H2AX and 8-OHG immunohistochemistry has been evaluated on duodenal biopsies of celiac subjects and controls.
Results: Gliadin induced a significant increase (+50%) of ROS after 12 h of exposition starting with a 500 μg/mL dose of gliadin. Comet assay and γ-H2AX demonstrated DNA damage, evident at the gliadin concentration of 500 μg/mL after 24 h. TG2 activity increased in chromatin and cytoskeleton cellular compartments at different gliadin doses (250/500/1000 μg/mL). The γ-H2AX and 8-OHG immunohistochemistry was altered in the duodenal biopsies of celiac patients.
Conclusions: Gliadin induces cellular oxidative stress, DNA damage and pro-apoptotic stimulation in Caco-2 cells and in the duodenal mucosa of celiac patients.
(Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
