Iron-Ascorbate-Mediated Lipid Peroxidation Causes Epigenetic Changes in the Antioxidant Defense in Intestinal Epithelial Cells: Impact on Inflammation

Sabrina Yara, Jean Claude Lavoie, Jean François Beaulieu, Edgard Delvin, Devendra Amre, Valerie Marcil, Ernest Seidman, Emile Levy

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction:The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury. Intraluminal pro-oxidants from ingested nutrients especially iron salts and ascorbic acid frequently consumed together, can lead to catalytic formation of oxygen-derived free radicals that ultimately overwhelm the cellular antioxidant defense and lead to cell damage.Hypothesis:Since the mechanisms remain sketchy, efforts have been exerted to evaluate the role of epigenetics in modulating components of endogenous enzymatic antioxidants in the intestine. To this end, Caco-2/15 cells were exposed to the iron-ascorbate oxygen radical-generating system.Results:Fe/Asc induced a significant increase in lipid peroxidation as reflected by the elevated formation of malondialdehyde along with the alteration of antioxidant defense as evidenced by raised superoxide dismutase 2 (SOD2) and diminished glutathione peroxidase (GPx) activities and genes. Consequently, there was an up-regulation of inflammatory processes illustrated by the activation of NF-κB transcription factor, the higher production of interleukin-6 and cycloxygenase-2 as well as the decrease of IκB. Assessment of promoter's methylation revealed decreased levels for SOD2 and increased degree for GPx2. On the other hand, pre-incubation of Caco-2/15 cells with 5-Aza-2′-deoxycytidine, a demethylating agent, or Trolox antioxidant normalized the activities of SOD2 and GPx, reduced lipid peroxidation and prevented inflammation.Conclusion:Redox and inflammatory modifications in response to Fe/Asc -mediated lipid peroxidation may implicate epigenetic methylation.

Original languageEnglish (US)
Article numbere63456
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 22 2013

ASJC Scopus subject areas

  • General

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