Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells

Abstract

1) Background: Hyperglycemia leads to several biochemical and physiological consequences, such as the generation of advanced glycation end products (AGEs) and reactive oxygen species (ROS), which are involved in the development of several human diseases. Intestinal cells are continuously exposed to pro-oxidants and lipid peroxidation products from ingested foods, and also to glyco-oxidative damage. It has been reported that free radical generation may be linked to the development of inflammation-related gastrointestinal diseases.(2) Methods: The effects of high glucose (HG) treatment (50 mM) were assessed in terms of free radical production, lipid peroxidation, and AGEs formation. Furthermore, the expression and the antiapoptotic and antioxidant activity of the paraoxonase-2 (PON2) enzyme in intestinal cells has been investigated. (3) Results: Caco-2 cells treated with media supplied with high glucose (HG) (50 mM) showed, with respect to physiological glucose concentration (25 mM), an increase in ROS production, lipid peroxidation, and AGEs formation. Moreover, a lower PON2 expression and activity in HG-treated cells was related to activation of the apoptotic pathways. (4) Conclusions: Our results demonstrated that high glucose concentrations triggered glyco-oxidative stress in intestinal cells; the downregulation of PON2 could result in a higher oxidative stress and might contribute to intestinal dysfunction.

Protection of Polyphenols Against Glyco-Oxidative Stress: Involvement of Glyoxalase Pathway

“…Several studies have shown higher AGEs levels in HG condition [35,36]. As previously demonstrated, intestinal cells are sensitive to glycooxidative stress when exposed to high glucose concentrations [21]. Glyco-oxidative stress was confirmed in this study with an increase of AGEs formation, increase of intracellular ROS production, lipid peroxidation and a decrease of total antioxidant capacity.…”

“…Therefore, a growing interest is devoted to molecules able to decrease dicarbonyl stress targeting the glyoxalase system. Our recent study has shown that high glucose concentrations triggers an increase of levels of intracellular ROS, lipid peroxidation and formation of fluorescent AGEs and GA-modified proteins in intestinal cells [21]. In this study we investigated the effect of high glucose chronic exposure on glyco-oxidation and glyoxalase system in intestinal cells.…”

Protection of Polyphenols against Glyco-Oxidative Stress: Involvement of Glyoxalase Pathway

“…Many “in vivo” and “in vitro” studies have shown that there is a strong correlation between a hyperglycemia condition and the formation of AGEs [ 40 , 41 ]. As previously demonstrated, intestinal cells are sensitive to glyco-oxidative stress when exposed to high glucose concentrations [ 20 ]. Glyco-oxidative stress was confirmed in this study with an increase of AGEs formation, increase of intracellular ROS production, lipid peroxidation, and a decrease of total antioxidant capacity.…”

“…Cellular vitality was measured using Trypan Blue 0.1% exclusion assay. Cells were treated with culture medium containing 25 mM (control cells) or 50 mM glucose (high glucose, HG) concentrations for 1 week [ 20 ], in the absence or in the presence of apple extract containing two concentrations of polyphenols (0.4 mmol GAE/L and 0.8mmolGAE/L) [ 30 , 33 ]. Medium was replaced two times a week.…”

“…Therefore, a growing interest is devoted to molecules able to decrease dicarbonyl stress targeting the glyoxalase system. Our recent study has shown that high glucose concentration triggers an increase of levels of intracellular ROS, lipid peroxidation, and formation of fluorescent AGEs and GA-modified proteins in intestinal cells [ 20 ].…”