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.
Keywords
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Article info
Publication history
Published online: July 03, 2018
Accepted:
June 20,
2018
Received in revised form:
May 29,
2018
Received:
January 16,
2018
Identification
Copyright
© 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
