Development, Validity, and Reliability of a Food Frequency Questionnaire Eliciting the Dietary Advanced Glycation End Product Consumption among Obese Adolescents Aged 10-19 Years.

BACKGROUND: Obesity has reached an alarming rate affecting all categories of the population. A tremendous rise in obesity has been observed in children and adolescents. In India, the prevalence of adolescent obesity is more than 30% of the population. Advanced glycation end products (AGEs) are a diverse group of compounds formed by the amalgamation of glucose and a protein moiety. These glycated compounds are found in processed foods subjected to high-temperature cooking techniques contributing to the formation of dietary AGEs (dAGEs). The enormous consumption of dAGE attributes to the development of metabolic diseases. OBJECTIVES: The objective of this study was to develop and validate a food frequency questionnaire (FFQ) among obese adolescents aged 10-19 years to gauge their dAGE consumption. MATERIALS AND METHODS: This questionnaire was developed from previous literature (15 articles), validated using the content validity ratio (CVR) by Lawshe, and estimated for reliability using the test-retest method. A pilot study was done among 50 obese adolescents aged 10-19 years, who completed the questionnaire twice, with a gap of 15 days. RESULTS: A total of 54 items were validated (CVR ≥0.99) from the 60 food items. A reliability score >0.7 was observed, and a significant correlation (P ≥ 0.01) between the test and retest results was determined. CONCLUSION: Hence, this FFQ is reliable and can be used for future research studies to elicit dAGE consumption among obese adolescents.

Dang-Gui-Si-Ni decoction facilitates wound healing in diabetic foot ulcers by regulating expression of AGEs/RAGE/TGF-ß/Smad2/3.

Diabetic foot ulcer (DFU) is a predominant complication of diabetes mellitus with poor prognosis accompanied by high amputation and mortality rates. Dang-Gui-Si-Ni decoction (DSD), as a classic formula with a long history in China, has been found to improve DFU symptoms. However, mechanism of DSD for DFU therapy remains unclear with no systematic elaboration. In vivo, following establishment of DFU rat model, DSD intervention with low, medium and high doses was done, with Metformin (DM) as a positive control group. With wound healing detection, pathological changes by HE staining, inflammatory factor expression by ELISA and qRT-PCR, oxidative stress levels by ELISA, and AGEs/RAGE/TGF-ß/Smad2/3 expression by Western blot were performed. In vitro, intervention with LY2109761 (TGF-ß pathway inhibitor) based on DSD treatment in human dermal fibroblast-adult (HDF-a) cells was made. Cell viability by CCK8, migration ability by cell scratch, apoptosis by flow cytometry, and AGEs/RAGE/TGF-ß/Smad2/3 expression by Western blot were measured. DFU rats exhibited elevated AGEs/RAGE expression, whereas decreased TGF-ß1 and p-Smad3/Smad3 protein expression, accompanied by higher IL-1ß, IL-6, TNF-α levels, and oxidative stress. DSD intervention reversed above effects. Glucose induction caused lower cell viability, migration, TGF-ß1 and p-Smad3/Smad3 protein expression, with increased apoptosis and AGEs/RAGE expression in HDF-a cells. These effects were reversed after DSD intervention, and further LY2109761 intervention inhibited DSD effects in cells. DSD intervention may facilitate wound healing in DFU by regulating expression of AGEs/RAGE/TGF-ß/Smad2/3, providing scientific experimental evidence for DSD clinical application for DFU therapy.

Effectiveness of date seed on glycemia and advanced glycation end-products in type 2 diabetes: a randomized placebo-controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting more than 95% of people with diabetes. Traditionally, some medicinal plants have been considered as an effective approach in management of T2DM. This trial evaluated the effects of date seed powder (DSP) on glycemia indices and oxidative stress in T2DM patients. METHODS: In this trail, 43 patients with T2DM were randomized to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Levels of glycemic indices, lipolpolysaccharide (LPS), and soluble receptor for advanced glycation end products (s-RAGE), as well as other parameters associated with oxidative stress were assessed at baseline and after 8 weeks. Independent t-test and analysis of covariance (ANCOVA) were used for between-groups comparisons at baseline and the post-intervention phase, respectively. RESULTS: The results showed that supplementation with DSP significantly decreased HbA1c (-0.30 ± 0.48%), insulin (-1.70 ± 2.21 µU/ml), HOMA-IR (-1.05 ± 0.21), HOMA-B (-0.76 ± 21.21), lipopolysaccharide (LPS) (-3.68 ± 6.05 EU/mL), and pentosidine (118.99 ± 21.67 pg/mL) (P < 0.05, ANCOVA adjusted for baseline and confounding factors). On the other hand, DSP supplementation significantly increased total antioxidant capacity (TAC) (0.50 ± 0.26 mmol/L), superoxide dismutase (SOD) (0.69 ± 0.32 U/ml), and s-RAGE (240.13 ± 54.25 pg/mL) compared to the placebo group. FPG, hs-CRP, GPx, CML, and uric acid had no significant within- or between-group changes. CONCLUSION: Supplementation of DSP could be considered an effective strategy to improve glycemic control and oxidative stress in T2DM patients (Registration ID at www.irct.ir : IRCT20150205020965N10).

Glyoxal and methylglyoxal formation in chocolate and their bioaccessibility.

The objective of this study was to assess the effects of simulated digestion on the formation of α-dicarbonyl compounds (α-DCs) in chocolates. For that purpose, the concentrations of glyoxal and methylglyoxal in chocolates were determined through High-Performance Liquid Chromatography (HPLC) analysis before and after in vitro digestion. The initial concentrations ranged from 0.0 and 228.2 µg/100 g, and 0.0 and 555.1 for glyoxal and methylglyoxal, respectively. Following digestion, there was a significant increase in both glyoxal and methylglyoxal levels, reaching up to 1804 % and 859 %, respectively. The findings indicate that digestive system conditions facilitate the formation of advanced glycation end product (AGE) precursors. Also, glyoxal and methylglyoxal levels were found to be low in chocolate samples containing dark chocolate. In contrast, they were found to be high in samples containing hazelnuts, almonds, pistache, and milk. Further studies should focus on α-DCs formation under digestive system conditions, including the colon, to determine the effects of gut microbiota.

Proteomics-based identification of biomarkers reflecting endogenous and exogenous exposure to the advanced glycation end product precursor methylglyoxal in SH-SY5Y human neuroblastoma cells.

Methylglyoxal (MGO), a highly reactive precursor of advanced glycation end products, is endogenously produced and prevalent in various food products. This study aimed to characterize protein modifications in SH-SY5Y human neuroblastoma cells induced by MGO and identify potential biomarkers for its exposure and toxicity. A shot-gun proteomic analysis was applied to characterize protein modifications in cells incubated with and without exogenous MGO. Seventy-seven proteins were identified as highly susceptible to MGO modification, among which eight, including vimentin and histone H2B type 2-F, showing concentration-dependent modifications by externally added MGO, were defined as biomarkers for exogenous MGO exposure. Remarkably, up to 10 modification sites were identified on vimentin. Myosin light polypeptide 6 emerged as a biomarker for MGO toxicity, with modifications exclusively observed under cytotoxic MGO levels. Additionally, proteins like serine/threonine-protein kinase SIK2 and calcyphosin, exhibiting comparable or even higher modification levels in control compared to exogenous MGO-treated cells, were defined as biomarkers for endogenous exposure. Bioinformatics analysis revealed that motor proteins, cytoskeleton components, and glycolysis proteins were overrepresented among those highly susceptible to MGO modification. These results identify biomarkers for both endogenous and exogenous MGO exposure and provide insights into the cellular effects of endogenously formed versus externally added MGO.

Advanced glycation end product-modified low-density lipoprotein promotes pro-osteogenic reprogramming via RAGE/NF-κB pathway and exaggerates aortic valve calcification in hamsters.

BACKGROUND: Advanced glycation end product-modified low-density lipoprotein (AGE-LDL) is related to inflammation and the development of atherosclerosis. Additionally, it has been demonstrated that receptor for advanced glycation end products (RAGE) has a role in the condition known as calcific aortic valve disease (CAVD). Here, we hypothesized that the AGE-LDL/RAGE axis could also be involved in the pathophysiological mechanism of CAVD. METHODS: Human aortic valve interstitial cells (HAVICs) were stimulated with AGE-LDL following pre-treatment with or without interleukin 37 (IL-37). Low-density lipoprotein receptor deletion (Ldlr-/-) hamsters were randomly allocated to chow diet (CD) group and high carbohydrate and high fat diet (HCHFD) group. RESULTS: AGE-LDL levels were significantly elevated in patients with CAVD and in a hamster model of aortic valve calcification. Our in vitro data further demonstrated that AGE-LDL augmented the expression of intercellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and alkaline phosphatase (ALP) in a dose-dependent manner through NF-κB activation, which was attenuated by nuclear factor kappa-B (NF-κB) inhibitor Bay11-7082. The expression of RAGE was augmented in calcified aortic valves, and knockdown of RAGE in HAVICs attenuated the AGE-LDL-induced inflammatory and osteogenic responses as well as NF-κB activation. IL-37 suppressed inflammatory and osteogenic responses and NF-κB activation in HAVICs. The vivo experiment also demonstrate that supplementation with IL-37 inhibited valvular inflammatory response and thereby suppressed valvular osteogenic activities. CONCLUSIONS: AGE-LDL promoted inflammatory responses and osteogenic differentiation through RAGE/NF-κB pathway in vitro and aortic valve lesions in vivo. IL-37 suppressed the AGE-LDL-induced inflammatory and osteogenic responses in vitro and attenuated aortic valve lesions in a hamster model of CAVD.

Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.

Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.

Glycation resistance and life-history traits: lessons from non-conventional animal models.

Glycation reactions play a key role in the senescence process and are involved in numerous age-related pathologies, such as diabetes complications or Alzheimer's disease. As a result, past studies on glycation have mostly focused on human and laboratory animal models for medical purposes. Very little is known about glycation and its link to senescence in wild animal species. Yet, despite feeding on high-sugar diets, several bat and bird species are long-lived and seem to escape the toxic effects of high glycaemia. The study of these models could open new avenues both for understanding the mechanisms that coevolved with glycation resistance and for treating the damaging effects of glycations in humans. Our understanding of glycaemia's correlation to proxies of animals' pace of life is emerging in few wild species; however, virtually nothing is known about their resistance to glycation, nor on the relationship between glycation, species' life-history traits and individual fitness. Our review summarizes the scarce current knowledge on the links between glycation and life-history traits in non-conventional animal models, highlighting the predominance of avian research. We also investigate some key molecular and physiological parameters involved in glycation regulation, which hold promise for future research on fitness and senescence of individuals.

Fructosyl Amino Oxidase as a Therapeutic Enzyme in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.

Deciphering the inhibitory mechanisms of betanin and phyllocactin from Hylocereus polyrhizus peel on protein glycation, with insights into their application in bread.

Protein glycation closely intertwines with the pathogenesis of various diseases, sparking a growing interest in exploring natural antiglycation agents. Herein, high-purity betacyanins (betanin and phyllocactin) derived from Hylocereus polyrhizus peel were studied for their antiglycation potential using an in vitro bovine serum albumin (BSA)-glucose model. Notably, betacyanins outperformed aminoguanidine, a recognized antiglycation agent, in inhibiting glycation product formation across different stages, especially advanced glycation end-products (AGEs). Interestingly, phyllocactin displayed stronger antiglycation activity than betanin. Subsequent mechanistic studies employing molecular docking analysis and fluorescence quenching assay unveiled that betacyanins interact with BSA endothermically and spontaneously, with hydrophobic forces playing a dominant role. Remarkably, phyllocactin demonstrated higher binding affinity and stability to BSA than betanin. Furthermore, the incorporation of betacyanins into bread dose-dependently suppressed AGEs formation during baking and shows promise for inhibiting in vivo glycation process post-consumption. Overall, this study highlights the substantial potential of betacyanins as natural antiglycation agents.

Albumin Oxidation and Albumin Glycation Discordance During Type 2 Diabetes Therapy: Biological and Clinical Implications.

Aims: Cys34 albumin redox modifications (reversible "cysteinylation" and irreversible "di/trioxidation"), besides being just oxidative stress biomarkers, may have primary pathogenetic roles to initiate and/or aggravate cell, tissue, and vascular damage in diabetes. In an exploratory "proof-of-concept" pilot study, we examined longitudinal changes in albumin oxidation during diabetes therapy. Methods: Mass spectrometric analysis was utilized to monitor changes in human serum albumin (HSA) post-translational modifications {glycation [glycated albumin (GA)], cysteinylation [cysteinylated albumin (CA) or human non-mercaptalbumin-1; reversible], di/trioxidation (di/trioxidized albumin or human non-mercaptalbumin-2; irreversible), and truncation (truncated albumin)} during ongoing therapy. Four informative groups of subjects were evaluated [type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity, and healthy controls] at baseline, and subjects with diabetes were followed for a period up to 280 days. Results: At baseline, T2DM was associated with relatively enhanced albumin cysteinylation (CA% total) compared with T1DM (P = 0.004), despite comparable mean hyperglycemia (P values: hemoglobin A1c = 0.09; GA = 0.09). T2DM, compared with T1DM, exhibited selectively and significantly higher elevations of all the "individual" glycated cum cysteinylated ("multimodified") albumin isoforms (P values: CysHSA+1G = 0.003; CysHSA+2G = 0.007; and CysHSA+3G = 0.001). Improvements in glycemic control and decreases in albumin glycation during diabetes therapy in T2DM were not always associated with concurrent reductions of albumin cysteinylation, and in some therapeutic situations, albumin cysteinylation worsened (glycation-cysteinylation discordance). Important differences were observed between the effects of sulfonylureas and metformin on albumin molecular modifications. Conclusions: T2DM was associated with higher oxidative (cysteinylation) and combined (cysteinylation plus glycation) albumin molecular modifications, which are not ameliorated by improved glucose control alone. Further studies are required to establish the clinical significance and optimal therapeutic strategies to address oxidative protein damage and resulting consequences in diabetes.

Decoding the role of aldosterone in glycation-induced diabetic complications.

Diabetes-mediated development of micro and macro-vascular complications is a global concern. One of the factors is hyperglycemia induced the non-enzymatic formation of advanced glycation end products (AGEs). Accumulated AGEs bind with receptor of AGEs (RAGE) causing inflammation, oxidative stress and extracellular matrix proteins (ECM) modifications responsible for fibrosis, cell damage and tissue remodeling. Moreover, during hyperglycemia, aldosterone (Aldo) secretion increases, and its interaction with mineralocorticoid receptor (MR) through genomic and non-genomic pathways leads to inflammation and fibrosis. Extensive research on individual involvement of AGEs-RAGE and Aldo-MR pathways in the development of diabetic nephropathy (DN), cardiovascular diseases (CVDs), and impaired immune system has led to the discovery of therapeutic drugs. Despite mutual repercussions, the cross-talk between AGEs-RAGE and Aldo-MR pathways remains unresolved. Hence, this review focuses on the possible interaction of Aldo and glycation in DN and CVDs, considering the clinical significance of mutual molecular targets.

Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.

Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.

Effects of protein glycation and protective mechanisms against glycative stress.

Glycation is a posttranslational modification of proteins that contributes to the vast array of biological information that can be conveyed via a singular proteome. Understanding the role of advanced glycation end-products (AGEs) in human health and pathophysiology can be difficult, as the physiological effects of AGEs have been associated with multiple biological processes and disease state development, including acute myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis, as well as tumor cell migration. The critical role of the glyoxalase system in the detoxification of methylglyoxal and other AGEs has been well established. Recently, evidence has emerged that DJ-1 displays antiglycative activity and may contribute to another mechanism of protection against protein glycation outside of the glyoxalase system. Identification of potential substrates of DJ-1 and determination of the pathways in which DJ-1 operates, is needed to fully understand the role of this protein in modulating biological homeostasis and the development of disease.

Coffee leaf extract inhibits advanced glycation end products and their precursors: A mechanistic study.

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.

Berry anthocyanins prevent α-dicarbonyls and advanced glycation end product formation in phosphate-buffered saline-based model systems, cookie and ground pork.

α-Dicarbonyls and advanced glycation end products (AGEs) are the heat-induced potential toxicants commonly found in thermally processed foods due to the Maillard reaction. Research has shown that both α-dicarbonyls and AGEs can cause oxidative stress and inflammation and have a positive link with several chronic diseases, such as diabetes. This study found that commonly consumed berry fruits exhibited excellent methylglyoxal (MGO)-trapping and antiglycative activities, positively associated with their total phenolic and flavonoid contents. Blackcurrant exhibited the strongest MGO-trapping and antiglycative activities among the tested berry fruits. In addition, we demonstrated that fortification with blackcurrant significantly reduced α-dicarbonyls and AGEs formation in the chocolate cookies and marinated ground pork. Delphinidin and cyanidin glycosides were identified as the primary bioactive compounds of blackcurrant that trapped MGO to form the corresponding mono- and di-MGO adducts. This study suggested that blackcurrant anthocyanins might serve as a novel additive to reduce the consumption of dietary reactive carbonyl species and AGEs from both animal- and plant-derived processed foods. PRACTICAL APPLICATION: The levels of α-dicarbonyls and advanced glycation end products in ground pork and cookies were significantly reduced when fortified with blackcurrant. The blackcurrant anthocyanins might be a novel agent inhibiting α-dicarbonyls and dietary advanced glycation end products formation in thermally processed foods.

Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

BACKGROUND: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. METHODS: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (Nε-(carboxymethyl)lysine [CML], Nε-(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. RESULTS: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (-12%) and hypoxia-exposed placentas (-16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (-26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. CONCLUSIONS: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia.

Absorption and intracellular accumulation of food-borne dicarbonyl precursors of advanced glycation end-product in a Caco-2 human cell transwell model.

This study aimed to better understand whether and how the reactive 1,2-dicarbonyl precursors of advanced glycation end products (AGEs), glyoxal (GO) and methylglyoxal (MGO), cross the intestinal barrier by studying their transport in the in vitro Caco-2 transwell system. The results reveal that GO, MGO and Nε-(carboxymethyl)lysine (CML), the latter studied for comparison, are transported across the intestinal cell layer via both active and passive transport and accumulate in the cells, albeit all to a limited extent. Besides, the transport of the dicarbonyl compounds was only partially affected by the presence of amino acids and protein, suggesting that scavenging by a food matrix will not fully prevent their intestinal absorption. Our study provides new insights into the absorption of the two major food-borne dicarbonyl AGE precursors and provides evidence of their potential systemic bioavailability but also of factors limiting their contribution to the overall exposome.

Trapping mechanism by di-d-psicose anhydride with methylglyoxal for prevention of diabetic nephropathy.

Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA-MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA-MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA-MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide.

Glycated LDL generates reactive species that damage cell components, oxidize hemoglobin and alter surface morphology in human erythrocytes.

Low-density lipoprotein (LDL) transports cholesterol to various tissues via the blood. Glycation of LDL occurs during hyperglycemic condition which is characterised by persistently high blood glucose level. Circulating erythrocytes can come in direct contact with glycated LDL (G-LDL). The objective of this study was to investigate the effect of G-LDL on human erythrocytes, specifically on hemoglobin, intracellular generation of reactive species and the antioxidant defence system. Isolated erythrocytes were incubated with G-LDL (3 and 6 mg/ml) and native LDL (6 mg/ml) at 37 °C for 24 h. Native LDL and G-LDL untreated erythrocytes were similarly incubated at 37 °C and served as control. G-LDL treatment increased hemolysis compared to control and native LDL-treated erythrocytes. Incubation of erythrocytes with G-LDL led to an increase in protein oxidation and lipid peroxidation while greatly decreasing the total sulfhydryl content. It also significantly enhanced hemoglobin oxidation, heme degradation, and the release of free iron moiety. Treatment with G-LDL led to an appreciable increase in the production of reactive oxygen and nitrogen species. The antioxidant power and activities of major antioxidant enzymes were drastically reduced, while critical membrane-bound enzymes were inhibited. The surface morphology of G-LDL-treated erythrocytes was altered leading to the formation of echinocytes. Importantly, treatment of erythrocytes with native LDL did not significantly affect the above-mentioned parameters and values were similar to the corresponding controls. Thus, G-LDL is cytotoxic to human erythrocytes and causes oxidative damage to cell components. This can reduce the oxygen-transporting ability of blood and also result in red cell senescence and anemia.