Abstract
IntroductionThe 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.HypothesisSince 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.ResultsFe/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.ConclusionRedox and inflammatory modifications in response to Fe/Asc -mediated lipid peroxidation may implicate epigenetic methylation.
Highlights
The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury
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
There was an up-regulation of inflammatory processes illustrated by the activation of nuclear factor-kB (NF-kB) transcription factor, the higher production of interleukin-6 and cycloxygenase-2 as well as the decrease of IkB
Summary
The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury. Various studies have evidenced their effectiveness as important signaling molecules that modulate gene expression, cell growth and survival, as well as oxygen sensing in various cell types [1,2] Their excessive formation leads to lasting oxidative stress (OxS), characterized by an imbalance between oxidant-producing systems and antioxidant defense mechanisms, which can trigger cell damage by oxidizing macromolecular structures (lipids, proteins and DNA) and causes cell death [3]. Depending on their cell concentrations, ROS can act as either beneficial or harmful biological agents that contribute to the development of chronic diseases, including osteoporosis, type 2 diabetes, neurodegenerative, cardiovascular disorders, and cancer [4]. Individual genetic variation may influence dietary antioxidant status in a fashion of gene-diet interactions and, the body’s ability to manage OxS [8]
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