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.
(1) Carthamus Tinctorius L. (safflower) is extensively used in traditional herbal medicine. (2) The aim of this study was to investigate the bioactive properties of polyphenol extracts from flowers of Carthamus Tinctorius (CT) cultivated in Italy. We also evaluated the properties of two bioactive water-soluble flavonoid compounds, hydroxy safflor yellow A (HSYA) and safflor yellow A (SYA), contained in Carthamus Tinctorius petals. (3) The total polyphenol content was 3.5 ± 0.2 g gallic acid equivalent (GAE)/100 g, flavonoids content was 330 ± 23 mg catechin equivalent (CE)/100 g in the flowers. The extract showed a high antioxidant activity evaluated by oxygen radical absorbance capacity (ORAC) and 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assays. In addition, flower extract, SYA, and HSYA were able to reduce the susceptibility of low-density lipoprotein to copper-induced lipid peroxidation. In order to investigate the bioactive properties of flower extract, SYA, and HSYA we also studied their modulatory effect of oxidative stress on human dermal fibroblasts (HuDe) oxidized by tert-butyl hydroperoxide (t-BOOH). The CT extract at concentrations ranging from 0.01–20 μg GAE/mL of polyphenols, exerted a protective effect against t-BOOH triggered oxidative stress. At higher concentration the extract exerted a pro-oxidant effect. Similar results have been obtained using HSYA and SYA. (4) These results demonstrate a biphasic effect exerted by HSYA, SYA, and flower extracts on oxidative stress.
Products obtained using 100% legume flours (pea, red lentil, chickpea, grass pea) contain elevated levels of healthy functional components and have a low glycaemic index.
Aim of the study was to characterize the nutritional composition of 11 apple varieties including 9 varieties from the Regional Repertory of Biodiversity of Marche (Italy). The qualitative and quantitative profiles of polyphenols were evaluated through HPLC‐DAD‐MS analysis. Antioxidant properties were evaluated by 1,1‐diphenyl‐2‐picrilhydrazyl, ferric reducing antioxidant power, and oxygen radical absorbance capacity assays. The ability of apple extracts to inhibit glyco‐oxidative stress was studied using three experimental models: albumin glycated by incubation with fructose or methylglyoxal and human dermal fibroblasts incubated with high‐glucose (HG) concentration. The results demonstrated a variability in polyphenolic profile, radical scavenging capacity, and ability to inhibit non‐enzymatic glycation of protein. The results showed that HG treatment increased the formation of reactive oxygen species, lipid hydroperoxides, and advanced glycation end products in cells with a decrease in total antioxidant capacity. Apple extracts were able to counteract the glycoxidizing action of high glucose, the protective effect was related to apple polyphenol content. Practical applications Local apple varieties could be considered as an important source of genes for apple breeding program and as preferable sources for the development of apple‐based food with a strong focus on health beneficial effects. Information about the health‐promoting components of ancient varieties may be important for the valorization and preservation of local cultivars, which may represent an important impulse to revitalize the agricultural economy in peripheral areas.
Objective High-density lipoproteins (HDL) exert pleiotropic roles in follicular fluid (FF). Previous studies have reported a relationship between obesity, infertility, and systemic oxidative stress. The aim of our study was to investigate for the first time the HDL functional properties in FF in obesity. Methods In this observational study, overweight/obese (n = 20) and normal-weight women (n = 38) undergoing assisted reproductive technology were included. Compositional properties and biochemical marker of functionality (HDL oxidation rate), HDL-associated antioxidants (paraoxonase-1 activities and CoQ10 content), and lipid hydroperoxide levels were evaluated in FF from normal-weight and overweight/obese women. Correlations between biochemical parameters and indices for oocyte and embryo quality were studied. Results FF-HDL obtained from overweight/obese women are characterized by high intrinsic ability to be oxidized compared with FF-HDL from normal-weight women. These alterations are associated with lower activities of paraoxonase-1 (PON1), higher levels of lipid peroxidation, and a lower total antioxidant capacity in FF. Moreover, an association between PON1 activity and FF-HDL oxidation and clinical parameter of oocyte quality was observed. Conclusion Our data suggest that the quality of FF-HDL is important determinant for oocyte quality. Therefore, targeting FF-HDL functionality, in addition to FF-HDL-C levels, may represent a promising and interesting biomarker for reproductive outcomes.
The goal of the current study was to identify potential roles of paraoxonase-2 in bladder carcinogenesis. T24 bladder cancer cells were transfected with plasmids inducing paraoxonase-2 silencing or overexpression. Upon the selection of clones stably down- or upregulating paraoxonase-2, cell proliferation, migration, and the production of reactive oxygen species were evaluated, before and after treatment with cisplatin and gemcitabine, used alone or in combination. The activity levels of both caspase-3 and caspase-8 were also analyzed. shRNA-mediated gene silencing and the overexpression of paraoxonase-2 revealed that the enzyme was able to promote both the proliferation and migration of T24 cells. Moreover, the knockdown of paraoxonase-2 was significantly associated with a reduced cell viability of T24 cells treated with chemotherapeutic drugs and led to both an increase of reactive oxygen species production and caspase-3 and caspase-8 activation. Conversely, under treatment with anti-neoplastic compounds, a higher proliferative capacity was found in T24 cells overexpressing paraoxonase-2 compared with controls. In addition, upon enzyme upregulation, both the production of reactive oxygen species and activation of caspase-3 and caspase-8 were reduced. Although further analyses will be required to fully understand the involvement of paraoxonase-2 in bladder tumorigenesis and in mechanisms leading to the development of chemoresistance, the data reported in this study seem to demonstrate that the enzyme could exert a great impact on tumor progression and susceptibility to chemotherapy, thus suggesting paraoxonase-2 as a novel and interesting molecular target for effective bladder cancer treatment.
Chronic high glucose (HG) exposure increases methylglyoxal (MGO)-derived advanced glycation end-products (AGEs) and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic-degenerative diseases. Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is implicated in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. Aims of the study were to investigate the effects of HG-chronic exposure on glyco-oxidation and glyoxalase system in intestinal cells, using CaCo-2 cells. Moreover, we studied the effect of apple polyphenols on glyco-oxidative stress. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significant increase in intracellular Reactive Oxygen Species (ROS), lipid peroxidation, AGEs, and increase of Glyoxalase I (GlxI) activity. On the contrary, Glyoxalase II (GlxII) activity was lower in HG-treated cells. We demonstrate that apple polyphenols exert a protective effect against oxidative stress and dicarbonyl stress. The increase of total antioxidant capacity and glutathione (GSH) levels in HG-treated cells in the presence of apple polyphenols was associated with a decrease of GlxI activity.
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