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.

Gliadin effect on the oxidative balance and DNA damage : an in-vitro, ex-vivo study / E. Monguzzi, L. Marabini, L. Elli, V. Vaira, S. Ferrero, F. Ferretti, F. Branchi, G. Gaudioso, A. Scricciolo, V. Lombardo, L. Doneda, L. Roncoroni. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - 28:11(2018 Nov), pp. 1148-1154. [10.1016/j.dld.2018.06.020]

Gliadin effect on the oxidative balance and DNA damage : an in-vitro, ex-vivo study

E. Monguzzi;L. Marabini;L. Elli
;
V. Vaira;S. Ferrero;F. Ferretti;F. Branchi;G. Gaudioso;L. Doneda;L. Roncoroni
2018-11

Abstract

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.
Apoptosis; DNA damage; Oxidative stress; PT gliadin; Hepatology; Gastroenterology
Settore BIO/13 - Biologia Applicata
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/605527
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