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.
Highlights
Intestinal cells are highly vulnerable to oxidative damage due to the exposure to luminal oxidants and lipid peroxidation products from ingested foods [1,2,3,4]
Intracellular reactive oxygen species (ROS) levels, evaluated using carboxy-H2 DCFDA, were significantly increased after treatment with high glucose (HG-cells) compared with control cells (p < 0.001); a significant decrease of total intracellular antioxidant activity was observed in High Glucose (HG) cells compared with control (p < 0.001) (Figure 1)
Levels of lipid peroxidation products (TBARS levels) and fluorescent advanced glycation end products (AGEs) were significantly higher in HG-treated cells in comparison to control cells (Figure 2A)
Summary
Intestinal cells are highly vulnerable to oxidative damage due to the exposure to luminal oxidants and lipid peroxidation products from ingested foods [1,2,3,4]. It has been reported that reactive oxygen species (ROS) generation and alterations of antioxidant defense mechanisms may be linked to the development of gastrointestinal diseases such as inflammatory bowel disease (IBD) [1,2,3,4,5,6]. It has been observed that high levels of reactive oxygen (ROS) and nitrogen (RNS) species contribute to cell and tissue dysfunction and damage. ROS can behave as signaling molecules that regulate a wide variety of physiological functions: inducing programmed cell death or necrosis; inducing or suppressing the expression of many genes, and activating cell signaling cascades [7,8,9]. ROS can lead to the disruption of cell signaling transduction pathways. The translocation of transcription factors to the nucleus to the antioxidant response element (ARE)
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