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The prevalence of high-sugar diets and unhealthy habits exacerbates the production of advanced glycation end products (AGEs) in the body. When AGEs excessively accumulate in the body, they accelerate the aging process while directly or indirectly causing other complications that can seriously damage the body. Prevention of glycation damage is gaining increasing attention; however, a systematic strategy to combat glycation and specific glycation inhibitors is still lacking. By analyzing the process of glycation damage, we suggest that glycation damage can be mitigated by the inhibition of AGEs production, binding to proteins, and binding to receptors for advanced glycation end products, as well as the attenuation of downstream linkage reactions. This review summarizes the process of glycation damage. According to each step of the process, the review presents the corresponding anti-glycation strategies. Based on recent anti-glycation studies, we support the fabrication of glycation inhibitors by using natural plant products and fermentation products of lactic acid bacteria that partially exhibit anti-glycation properties. This review summarizes the mechanisms by which these dietary ingredients perform anti-glycation functions, providing relevant research evidence. We hope that this review will support and assist subsequent investigations in the development of anti-glycation inhibitors. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs), the products of non-enzymatic browning reactions between the active carbonyl groups of reducing sugars and the free amines of amino acids, are largely considered oxidative derivatives resulting from diabetic hyperglycemia, which are further recognized as a potential risk for insulin resistance (IR) and type 2 diabetes (T2D). The accumulation of AGEs can trigger numerous negative effects such as oxidative stress, carbonyl stress, inflammation, autophagy dysfunction and imbalance of gut microbiota. Recently, studies have shown that cereal polyphenols have the ability to inhibit the formation of AGEs, thereby preventing and alleviating T2D. In the meanwhile, phenolics compounds could produce different biological effects due to the quantitative structure activity-relationship. This review highlights the effects of cereal polyphenols as a nonpharmacologic intervention in anti-AGEs and alleviating T2D based on the effects of oxidative stress, carbonyl stress, inflammation, autophagy, and gut microbiota, which also provides a new perspective on the etiology and treatment of diabetes. [ABSTRACT FROM AUTHOR]

The term "glycation compounds" comprises a wide range of structurally diverse compounds that are formed endogenously and in food via the Maillard reaction, a chemical reaction between reducing sugars and amino acids. Glycation compounds produced endogenously are considered to contribute to a range of diseases. This has led to the hypothesis that glycation compounds present in food may also cause adverse effects and thus pose a nutritional risk to human health. In this work, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) summarized data on formation, occurrence, exposure and toxicity of glycation compounds (Part A) and systematically assessed potential associations between dietary intake of defined glycation compounds and disease, including allergy, diabetes, cardiovascular and renal disease, gut/gastrotoxicity, brain/cognitive impairment and cancer (Part B). A systematic search in Pubmed (Medline), Scopus and Web of Science using a combination of keywords defining individual glycation compounds and relevant disease patterns linked to the subject area of food, nutrition and diet retrieved 253 original publications relevant to the research question. Of these, only 192 were found to comply with previously defined quality criteria and were thus considered suitable to assess potential health risks of dietary glycation compounds. For each adverse health effect considered in this assessment, however, only limited numbers of human, animal and in vitro studies were identified. While studies in humans were often limited due to small cohort size, short study duration, and confounders, experimental studies in animals that allow for controlled exposure to individual glycation compounds provided some evidence for impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to dicarbonyl compounds, albeit at dose levels by far exceeding estimated human exposures. The overall database was generally inconsistent or inconclusive. Based on this systematic review, the SKLM concludes that there is at present no convincing evidence for a causal association between dietary intake of glycation compounds and adverse health effects. EXECUTIVE SUMMARY: Considering the implication of endogenous glycation compounds in aging and disease, dietary exposure via consumption of an "AGE (advanced glycation end product) rich diet" is increasingly suggested to pose a potential health risk. However, studies attempting to assess an association between dietary glycation compounds and adverse health effects frequently suffer from insufficient chemical analysis of glycation compounds, including inadequate structural characterization and limited quantitative data. The Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) previously defined quality criteria for studies designed to assess the effects of dietary glycation compounds on human health. The aim of the present work is to summarize data on formation, occurrence, exposure and toxicity of glycation compounds (Part A) and to systematically evaluate if the currently available scientific database allows for a conclusive assessment of potential health effects of defined glycation compounds (Part B). The term "glycation compounds" comprises a wide range of structurally diverse compounds that derive from the Maillard reaction, a chemical reaction between reducing carbohydrates and amino compounds that occurs during food processing. In the first stage of the Maillard reaction, reducing sugars such as glucose and fructose react for instance with the ε-amino group of lysine, which is most abundant in food ("glycation" of lysine). Subsequently, these primary reaction products undergo Amadori rearrangement to yield products (ARP) such as fructosyllysine (FL) from glucose and also Heyns rearrangement products (HRPs) such as glucosyl- and mannosyllysine from fructose. While ARPs are rapidly formed during food processing, they are not stable and undergo degradation reactions, predominantly to 1,2-dicarbonyl compounds such as glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3-DG), which are highly reactive. The last stage of the Maillard reaction is characterized predominantly by the reaction of these dicarbonyl compounds with nucleophilic groups of proteins. The side-chains of lysine and arginine residues as well as the N-termini of proteins are important reaction sites. Carboxyalkylated amino acids such as N-ε-carboxymethyllysine (CML) and N-ε-carboxyethyllysine (CEL) result from reaction of the ε-amino group of lysine with the dicarbonyl compounds GO and MGO. Dicarbonyl compounds with C5 or C6 chains can form cyclic pyrrole derivatives at the ε-amino group of lysine. The most important example for this reaction is pyrraline, which is formed from reaction of 3-DG and lysine. The reaction of dicarbonyl compounds with the guanidino group of arginine mainly leads to hydroimidazolones, of which the MGO-derived hydroimidazolone 1 (MG-H1) is best described in food systems. ARPs are the most abundant glycation products found in food. Up to 55% of the lysine residues in food may be modified to ARPs at the side-chain. Food items particularly rich in ARPs include bread, rusk, biscuits, chocolate, and powdered infant formulas. Exposure estimates range between 0.6–1.6 mg/kg body weight (bw), although exposure may be as high as 14.3 mg/kg bw in individuals consuming foods with extreme ARP concentrations. Foods particularly rich in dicarbonyl compounds include heat-treated or long-term stored items rich in reducing sugars such as jams, alternative sweeteners, soft drinks, honey, candies, cookies, and vinegars, especially balsamico-type vinegars. The main contributors to the daily intake of MGO, GO, and 3-DG are coffee and bread. Dietary exposure to dicarbonyl compounds has been estimated to range between 0.02–0.29 mg/kg bw/d for MGO, 0.04–0.16 mg/kg bw/d for GO, 0.14–2.3 mg/kg bw/d for 3-DG, and 0.08–0.13 mg/kg bw/d for 3-deoxygalactosone (3-DGal). Dietary intake of 5-hydroxymethylfurfural (HMF), which can be formed from 3-DG, is estimated to range between 0.0001–0.9 mg/kg bw/d. Exposure estimates for individual glycated amino acids range from 0.03–0.35 mg/kg bw/d for CML, 0.02–0.04 mg/kg bw/d for CEL and 0.19–0.41 mg/kg bw/d for MG-H1. From a model diet consisting of 1 L milk, 500 g bakery products and 400 mL coffee, an intake of pyrraline corresponding to 0.36 mg/kg bw/d for a 70 kg person was estimated. Quantitative analysis of individual glycation compounds or their metabolites in tissues or body fluids as well as their reaction products with amino acids, proteins or DNA may serve to monitor exposure to glycation compounds. However, since glycation compounds are also formed endogenously, these biomarkers reflect the totality of the exposure, making it inherently difficult to define the body burden due to dietary intake against the background of endogenous formation. Information on the toxicokinetics and toxicity of glycation compounds is scarce and mostly limited to the reactive dicarbonyl compounds GO, MGO, 3-DG, HMF, and individual glycated amino acids such as CML and CEL. Acute toxicity of dicarbonyl compounds is low to moderate. There are some data to suggest that rapid detoxification of dicarbonyls in the gastrointestinal tract and liver may limit their oral bioavailability. Biotransformation of GO and MGO occurs predominantly via the glutathione (GSH)-dependent glyoxalase system, and to a lesser extent via glutathione-independent aldo-keto-reductases, which are also responsible for biotransformation of 3-DG. GO, MGO and 3-DG readily react with DNA bases in vitro, giving rise to DNA adducts. There is clear evidence for genotoxicity of GO, MGO and 3-DG. Repeated dose toxicity studies on GO consistently reported reduced body weight gain concomitant with reduced food and water consumption but did not identify compound related changes in clinical chemistry and hematology or histopathological lesions. There is also no evidence for systemic carcinogenicity of GO and MGO based on the available studies. However, initiation/promotion studies indicate that oral exposure to GO may exhibit genotoxic and tumor promoting activity locally in the gastrointestinal tract. From a 2-year chronic toxicity and carcinogenicity study in rats, a NOAEL for systemic toxicity of GO administered via drinking water of 25 mg/kg bw was reported based on reduced body weight and erosions/ulcer in the glandular stomach. Other non-neoplastic and neoplastic lesions were not observed. Acute toxicity of HMF is also low. From a 90-day repeated dose toxicity study in mice, a NOAEL of 94 mg/kg bw was derived based on cytoplasmic alterations of proximal tubule epithelial cells of the kidney. HMF was mostly negative in in vitro genotoxicity tests, although positive findings for mutagenicity were obtained under conditions that promote formation of the chemically reactive sulfuric acid ester 5-sulfoxymethylfurfural. There is some evidence of carcinogenic activity of HMF in female B6C3F1 mice based on increased incidences of hepatocellular adenoma, but not in male mice and rats of both sexes. Although data on oral bioavailability of glycated amino acids are mostly limited to CML, it appears that glycated amino acids may be absorbed from the gastrointestinal tract after oral exposure to their free and protein bound form. Glycated amino acids that are not absorbed in the intestine may be subject to metabolism by the gut microbiome. Glycated amino acids present in the systemic circulation are rapidly eliminated via the urine. Acute oral toxicity of CML is low. Studies in mice and rats reported changes in clinical chemistry parameters indicative of impaired renal and hepatic function. However, these changes were not dose-related and not supported by histopathological evaluation. Previous risk assessments of individual glycation compounds did not identify a health concern at estimated human exposures (GO, HMF) but also noted the lack of data to draw firm conclusions on health risks associated with exposure to MGO. To identify potential associations between dietary intake of defined glycation compounds and disease a systematic review was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) model, applying the quality criteria previously defined by the SKLM. Using a combination of keywords defining individual glycation compounds and relevant disease patterns linked to the subject area of food, nutrition and diet, a systematic search in Pubmed (Medline), Scopus and Web of Science was performed. Although the present systematic review identified numerous studies that investigated an association between an "AGE-rich diet" and adverse health effects, only a subset of studies was found to comply with the quality criteria defined by the SKLM and was thus considered suitable to assess potential health risks of dietary glycation compounds. For each adverse health effect considered in this assessment, only limited numbers of human studies were identified. Although studies in humans offer the advantage of investigating effects at relevant human exposures, these studies did not provide compelling evidence for adverse effects of dietary glycation compounds. Animal studies identified in this systematic review provide some evidence for induction of impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to GO and MGO as representatives of dicarbonyl compounds. Only limited evidence points to a link between high intake of glycated amino acids and metabolic disorders. However, these effects were typically reported to occur at dose levels that exceed human dietary exposure, often by several orders of magnitude. Unfortunately, most studies employed only one dose level, precluding characterization of dose-response and derivation of a point of departure for risk assessment. While in vitro studies provide some evidence for a potential mechanistic link between individual glycation compounds and presumed adverse health effects, the clinical and toxicological relevance of the in vitro findings is often limited by the use of high concentrations of glycation compounds that by far exceed human dietary exposure and by insufficient evidence for corresponding adverse effects in vivo. A key question that has not been adequately considered in most studies investigating systemic effects of glycation compounds is the extent of oral bioavailability of dietary glycation compounds, including the form in which MRPs may be taken up (e.g. free vs. peptide bound glycated amino acids). Understanding how much dietary glycation compounds really add to the significant endogenous background is critical to appraise the relevance of dietary MRPs for human health. While it appears mechanistically plausible that glycation of dietary allergens may affect their allergenic potential, the currently available data do not support the hypothesis that dietary glycation compounds may increase the risk for diet-induced allergies. There are no human studies addressing the immunological effects of dietary AGEs. Accordingly, there are no data on whether dietary AGEs promote the development of allergies, nor whether existing allergies are enhanced or attenuated. In numerous in vitro studies, the IgG/E binding ability of antigens and therefore their allergenic potential has been predominantly reported to be reduced by glycation. However, some in vitro studies showed that glycated proteins bind to receptors of immunological cells, and thus may have promoting effects on immune response and inflammation. Although experimental data from animal studies provide some evidence that high doses of individual glycation compounds such as MGO and protein-bound CML may produce certain adverse health effects, including diabetogenic, cardiovascular, metabolic and renal effects, the doses required to achieve these effects by far exceed human dietary exposures. Of note, in the only long-term study identified, a high dose of MGO administered via drinking water to mice for 18 months had no adverse effects on the kidneys, cardiovascular system, or development of diabetes. Experimental data from animal studies provide evidence that high doses of defined glycation compounds such as MGO or protein-bound CML may affect glucose homeostasis. However, the doses required to produce these effects markedly exceed human dietary exposure. Results from human studies are inconclusive: Three short-term intervention studies suggested that diets rich in AGEs may impair glucose homeostasis, whereas one recent intervention study and two observational studies failed to show such an effect. For the cardiovascular system, there is some evidence from in vitro and in vivo studies that high concentrations of MRPs, well above the dietary exposure of humans, may enhance inflammation in the cardiovascular system, induce endothelial damage, increase blood pressure and increase the risk of thrombosis. Only a limited number of human intervention studies investigated potential effects of short-term exposure and longer-term effects of glycation compounds on the cardiovascular system, and yielded inconsistent results. The few observational studies available either found no association between dietary MRP intake and cardiovascular function or even reported beneficial effects. Therefore, currently no definitive conclusion on potential acute and chronic effects of dietary MRPs on inflammation and cardiovascular function can be drawn. However, there is currently also no convincing evidence that potential adverse effects on the cardiovascular system are triggered by dietary MRP intake. Furthermore, human studies did not provide evidence for an adverse effect of dietary MRPs on kidney function. In animal studies with high levels of oral intake, MGO was reported to cause structural and functional effects in the kidney. Several studies show that the concentration of modified proteins and amino acids, such as CML, increases significantly in kidney tissue after oral intake. One study showed a negative effect of a high-temperature-treated diet containing increased CML concentrations on kidney structure integrity and impaired glomerular filtration. The causative relationship of accumulation of dietary MRPs and a functional decline of the kidneys, however, needs further confirmation. With regard to gut health, there is some evidence for alterations in gut microflora composition and the production of individual short-chain fatty acids (SCFAs) upon dietary exposure to glycation compounds. However, this has not been linked to adverse health effects in humans and may rather reflect adaptation of the gut microbiota to changing nutrients. In particular, a human observational study and several animal studies did not find a correlation between the intake of glycation compounds and increased intestinal inflammation. In animal studies, positive effects of glycation compounds on gut tissue damage and dysbiosis during colitis were described. Considering clear evidence for DNA reactivity and genotoxicity of the dicarbonyl compounds GO, MGO and 3-DG, it is plausible to suspect that dicarbonyl compounds may induce mutations and cancer. Although there is some evidence for tumor promoting activity of GO locally in the gastrointestinal tract, the only guideline-compatible chronic rodent bioassays reported erosions and ulcer in the glandular stomach but no treatment-related neoplastic lesions. A recent multinational cohort study with focus on CEL, CML, and MG-H1 found no evidence to support the hypothesis that dietary AGEs are linked to cancer risk. Evidence for an association between human exposure to dietary glycation compounds and detrimental effects on the brain and on cognitive performance is far from being compelling. No human studies fully complying with the defined quality criteria were identified. A few experimental studies reported neuroinflammation and cognitive impairment following dietary MRP exposure, but these can be considered indicative at best and do not support firm conclusions for human health. In addition to utilizing exceedingly high dosages of individual agents like CML, harsh processing conditions causing a multitude of major process-related changes do not allow to convincingly reconcile effects observed with measured/supposed contents of free and protein-bound CML alone. Overall, although dietary glycation compounds have been claimed to contribute to a wide range of adverse health effects, the present critical evaluation of the literature allows the conclusion that the available data are insufficient, inadequate or inconclusive and do not compellingly support the hypothesis of human health risks being related to the presence of glycation compounds in food. The study limitations detailed above, together with the fact that a large number of studies did not comply with the defined quality criteria and therefore had to be excluded highlight the importance of performing adequately designed human or animal studies to inform scientifically reliable health risk assessment. To achieve this, high quality, dependable scientific cooperation within various disciplines is pivotal. [ABSTRACT FROM AUTHOR]

Maillard reaction is a non-enzymatic thermal reaction during food processing and storage. It massively contributes to the flavor, color, health benefits and safety of foods and could be briefly segmented into initial, intermediate and final stages with the development of a cascade of chemical reactions. During thermal reaction of food ingredients, sugar, protein and amino acids are usually the main substrates, and polyphenols co-existed in food could also participate in the Maillard reaction as a modulator. Polyphenols including flavan-3-ols, hydroxycinnamic acids, flavonoids, and tannins have shown various effects throughout the process of Maillard reaction, including conjugating amino acids/sugars, trapping α-dicarbonyls, capturing Amadori rearrangement products (ARPs), as well as decreasing acrylamide and 5-hydroxymethylfurfural (5-HMF) levels. These effects significantly influenced the flavor, taste and color of processed foods, and also decreased the hazard products' level. The chemical mechanism of polyphenols-Maillard products involved the scavenging of radicals, as well as nucleophilic addition and substitution reactions. In the present review, we concluded and discussed the interaction of polyphenols and Maillard reaction, and proposed some perspectives for future studies. Food polyphenols regulate Maillard reaction through substrates, initial, intermediate and final stages/products of Maillard reaction. The trapping ability of food polyphenols on α-dicarbonyls relied on the structural properties, and was also affected by reaction conditions such as pH value. Food polyphenols could act as potential inhibitors toward the formation of harmful compounds during advanced and final stages of Maillard reaction. The chemical mechanism of polyphenols-Maillard reaction products involved the scavenging of radicals, as well as nucleophilic addition and substitution. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) have received a great concern for their complexity, heterogeneity, and potential human risks. Dietary AGEs are considered as significant contributors to the body's AGE pool for increasing consumption of processed foods. AGEs are complex compounds derived from glycation or Maillard reaction between reducing sugars and amino acids during food processing. Precursors in raw materials and processing conditions play a crucial role in the formation of AGEs, which can be adjusted to restrict their generation. The addition of exogenous antioxidants is also a potential approach to decrease AGEs. To date, mounting evidence have shown that the accumulation of AGEs in most tissues can cause occurrences of various chronic diseases, such as diabetes, cardiovascular disease and chronic renal failure. Fortunately, some natural compounds including flavonoids, phenolic acid and plant extracts were proved to be good candidates for AGEs toxicity inhibitors. In this review, the contaminant exposure, formation mechanism and toxicity of AGEs in thermal-processed foods are systematically discussed. Furthermore, inhibitory measures from precursors, processing conditions and exogenous additives are proposed to minimize their production. In addition, the intervention of AGEs-induced damages by natural compounds was summarized, consequently providing strategies for controlling AGEs and safeguarding food safety. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are formed in non-enzymatic reaction, oxidation, rearrangement and cross-linking between the active carbonyl groups of reducing sugars and the free amines of amino acids. The Maillard reaction is related to sensory characteristics in thermal processed food, while AGEs are formed in food matrix in this process. AGEs are a key link between carbonyl stress and neurodegenerative disease. AGEs can interact with receptors for AGEs (RAGE), causing oxidative stress, inflammation response and signal pathways activation related to neurodegenerative diseases. Neurodegenerative diseases are closely related to gut microbiota imbalance and intestinal inflammation. Polyphenols with multiple hydroxyl groups showed a powerful ability to scavenge ROS and capture α-dicarbonyl species, which led to the formation of mono- and di- adducts, thereby inhibiting AGEs formation. Neurodegenerative diseases can be effectively prevented by inhibiting AGEs production, and interaction with RAGEs, or regulating the microbiota-gut-brain axis. These strategies include polyphenols multifunctional effects on AGEs inhibition, RAGE-ligand interactions blocking, and regulating the abundance and diversity of gut microbiota, and intestinal inflammation alleviation to delay or prevent neurodegenerative diseases progress. It is a wise and promising strategy to supplement dietary polyphenols for preventing neurodegenerative diseases via AGEs-RAGE axis and microbiota-gut-brain axis regulation. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are generated in all stages of food thermal treatment. In order to reveal the inhibitory mechanism of AGEs, a range of concentration of (−)-epigallocatechin-3-gallate (EGCG) has been added during low-temperature vacuum heating (LTVH), and high-resolution mass spectrometry-based proteomics was applied for identifying and quantifying N-glycosylated proteins, N-glycosylated peptides, and N-glycosylated sites. The results indicated that, compared with atmospheric cooking, LTVH significantly decreased the generation of AGEs. The addition of EGCG has a positive effect on the inhibition of AGEs when the concentration is lower than 2,000 μg/mL, and 200 μg/mL was the optimal concentration. [ABSTRACT FROM AUTHOR]

Increased intake of Western diets and ultra-processed foods is accompanied by increased intake of advanced glycation end products (AGEs). AGEs can be generated exogenously in the thermal processing of food and endogenously in the human body, which associated with various chronic diseases. In food, AGEs can be divided into free and bound forms, which differ in their bioavailability, digestion, absorption, gut microbial interactions and untargeted metabolites. We summarized the measurements and contents of free and bound AGE in foods. Moreover, the ingestion, digestion, absorption, excretion, gut microbiota interactions, and metabolites and metabolic pathways between free and bound AGEs based on animal and human studies were compared. Bound AGEs were predominant in most of the selected foods, while beer and soy sauce were rich in free AGEs. Only 10%–30% of AGEs were absorbed into the systemic circulation when orally administered. The excretion of ingested free and bound AGEs was approximately 90% and 60%, respectively. Dietary free CML has a detrimental effect on gut microbiota composition, while bound AGEs have both detrimental and beneficial impacts. Free and bound dietary AGEs changed amino acid metabolism, energy metabolism and carbohydrate metabolism. And besides, bound dietary AGEs altered vitamin metabolism, and glycerolipid metabolism. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs) favor inflammation and oxidative stress, playing a role in chronic diseases pathogenesis. Grape polyphenols exert antiglycative and antioxidant effects which may contribute to prevent chronic diseases. However, clinical evidence of grape polyphenols on chronic disease prevention and treatment by glycation markers modulation are limited. Therefore, we aimed to critically analyze studies about that topic to investigate the antiglycative power of dietary grape polyphenol, and to explore the molecular mechanism involved. This systematic review was conducted and reported according to PRISMA guidelines. The following search terms were used: "grape", "extract", "grape seed extract", "grape skin extract", "polyphenol extract", "grape polyphenol(s)", "grape juice", "resveratrol", "quercetin", "catechin", "epicatechin", "procyanidin(s)", and "anthocyanin(s)". Seven studies were included. Glycated hemoglobin was not affected. The interventions duration may not have been enough to detect changes. Grape polyphenols reduced fructosamine and methylglyoxal (MGO) concentrations, and increased endogenous secretory RAGE (esRAGE) gene expression but did not affect the serum concentration. Resveratrol antiglycative effects are mainly due its ability to trap MGO and downregulate RAGE. In conclusion, grape polyphenols may have a positive impact on early glycation products, AGEs and esRAGE. Future studies are needed to explore how they modulate AGEs and receptors in chronic diseases. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) in food products may bring health risks. Meat is a rich source of AGEs due to high protein and fat content, and thermal processing and storage further accelerate the formation of AGEs in meat. However, there is no comprehensive review of the formation of AGEs in meat during processing and storage. This paper summarized the types, structures and the formation of AGEs in meat during processing and storage. Meanwhile, the pathologic effects of AGEs and the inhibition of AGEs generation were also highlighted. Finally, the remaining limitations and future research directions about AGEs were discussed. The review of AGEs has important implications for food and human health. Although great progress has been made both in medicine and food science about AGEs, more valuable references and suggestions for AGEs to people should be provided in the future. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS), i.e. a cluster of physiological and biochemical abnormalities can lead to diabetic nephropathy (DN). Insulin resistance, impaired fasting glucose are the main signs and symptoms of MetS. Excess sugar can induce various substantial structural changes like formation of advanced glycation end products (AGEs). AGEs are formed due to reaction of reducing sugars with amino groups of proteins, lipids and nucleic acids. AGEs when bound to the receptor for advanced glycation end products (RAGE) activate increased production of pro-inflammatory markers like interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) along with induction of endoplasmic reticulum (ER) stress. Accumulation of AGEs, enhanced reactive oxygen species (ROS) generation and activation of protein kinase C (PKC), are considered to induce glomerular hypertrophy, podocyte apoptosis, therefore contributing to the development and progression of DN. In this review, we decipher different biochemical and physiological factors that link AGEs and DN. [ABSTRACT FROM AUTHOR]

Podocyte injury leading to albuminuria is a characteristic feature of diabetic nephropathy (DN). Hyperglycemia and advanced glycation end products (AGEs) are major determinants of DN. However, the underlying mechanisms of podocyte injury remain poorly understood. The cytosolic protein TNFAIP2/M-Sec is required for tunneling nanotubes (TNTs) formation, which are membrane channels that transiently connect cells, allowing organelle transfer. Podocytes express TNFAIP2 and form TNTs, but the potential relevance of the TNFAIP2-TNT system in DN is unknown. We studied TNFAIP2 expression in both human and experimental DN and the renal effect of tnfaip2 deletion in streptozotocin-induced DN. Moreover, we explored the role of the TNFAIP2-TNT system in podocytes exposed to diabetes-related insults. TNFAIP2 was overexpressed by podocytes in both human and experimental DN and exposre of podocytes to high glucose and AGEs induced the TNFAIP2-TNT system. In diabetic mice, tnfaip2 deletion exacerbated albuminuria, renal function loss, podocyte injury, and mesangial expansion. Moreover, blockade of the autophagic flux due to lysosomal dysfunction was observed in diabetes-injured podocytes both in vitro and in vivo and exacerbated by tnfaip2 deletion. TNTs allowed autophagosome and lysosome exchange between podocytes, thereby ameliorating AGE-induced lysosomal dysfunction and apoptosis. This protective effect was abolished by tnfaip2 deletion, TNT inhibition, and donor cell lysosome damage. By contrast, Tnfaip2 overexpression enhanced TNT-mediated transfer and prevented AGE-induced autophagy and lysosome dysfunction and apoptosis. In conclusion, TNFAIP2 plays an important protective role in podocytes in the context of DN by allowing TNT-mediated autophagosome and lysosome exchange and may represent a novel druggable target. Abbreviations: AGEs: advanced glycation end products; AKT1: AKT serine/threonine kinase 1; AO: acridine orange; ALs: autolysosomes; APs: autophagosomes; BM: bone marrow; BSA: bovine serum albumin; CTSD: cathepsin D; DIC: differential interference contrast; DN: diabetic nephropathy; FSGS: focal segmental glomerulosclerosis; HG: high glucose; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LMP: lysosomal membrane permeabilization; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PI3K: phosphoinositide 3-kinase; STZ: streptozotocin; TNF: tumor necrosis factor; TNFAIP2: tumor necrosis factor, alpha-induced protein 2; TNTs: tunneling nanotubes; WT: wild type. [ABSTRACT FROM AUTHOR]

Background: As a repercussion of oxidative stress, reactive oxygen species augment the biochemical reaction of amino and carbohydrate groups of proteins, thus forming oxidative products known as Advanced Glycation End-products (AGEs), associated with acute coronary syndrome (ACS). Together, this milieu provokes oxidative stress and promotes the development of ACS. Methods: The studied cohort had 76 ACS individuals and 76 healthy controls. Blood samples of both groups were collected to measure the concentration of AGEs, Malondialdehyde (MDA), and the activity of antioxidants. Levels of lipid profile and inflammatory biomarkers were accessed in the study. The spectrophotometric ELISA kit was used to determine the levels of parameters. Result: The results indicated a significant increase in AGEs, MDA, LDL, and total cholesterol levels. Increased inflammatory markers, Intercellular adhesion molecule 1, and vascular cell adhesion proteins-1 in ACS patients were compared with the control subjects. A decrease is recorded in superoxide dismutase, HDL, and glutathione levels in ACS individuals. Conclusion: Our study demonstrated increased serum concentration of AGEs and several other factors, such as increased oxidative markers and, conversely, reduction in the antioxidant in ACS individuals. Therefore, we conclude these variables can be a potential biomarker in ACS individuals. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) lead to chronic oxidative stress and inflammation, which in turn augment diabetes complications. Resveratrol plays a potential role in relation to diabetes due to improving of hyperglycemia, oxidative stress, and inflammation. The aim of this review was to evaluate the scientific literature to identify the impacts of resveratrol on the accumulation of AGEs. The literature was searched in the online databases, viz. PubMed, SCOPUS, Embase, ProQuest, and Google Scholar until May 2019. From a total of 338 retrieved articles, 10 papers were eligible for the present analysis. Except one clinical trial, all studies were conducted on animals. All the included studies, except one, showed inhibitory effects of resveratrol on the accumulation of AGE or receptor for AGEs. The findings indicate that resveratrol is a potential protective agent against the accumulation of AGEs. There is, however, the need for future studies to investigate this effect on human. [ABSTRACT FROM AUTHOR]

To compare the advanced glycation end products (AGEs) levels in follicular fluid according to the different ovarian responses of women who underwent controlled ovarian stimulation due to unexplained infertility and to examine the relationship between these levels and pregnancy outcomes. Sixty-three women who underwent fresh IVF/ICSI cycles with GNRH antagonist protocol were divided into 3 groups according to the number of retrieved oocytes as suboptimal (4–9 oocytes), optimal (10–15 oocytes) and high (>15 oocytes) responders. AGEs levels in follicular fluid were measured by ELISA method. AGEs levels were 6.81 ± 2.20 µg/ml, 5.30 ± 2.01 and 6.44 ± 1.43 µg/ml in suboptimal, optimal and high response group, respectively. AGEs level was significantly higher in suboptimal response group than in optimal response group. The cutoff level of 6.19 µg/ml had a sensitivity of 59.3% and a specificity of 66.7% in distinguishing the suboptimal response group from the optimal response group. However, there were no statistically significant difference between AGEs levels and clinical pregnancy and live birth rates. Increased AGEs level in follicular fluid may be associated with decreased ovarian response during controlled ovarian stimulation in unexplained infertility case, however, it does not provide information about pregnancy outcomes [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are reactive chemical entities formed by non-enzymatic reaction between reducing sugars and amino group of proteins. Enhanced accumulation of AGEs and associated protein oxidation contribute to pathogenesis of diabetes-associated complications. Here, we evaluated the inhibitory activity of flavonoid compounds isolated from the leaves of Polyalthia longifolia on formation of AGEs and protein oxidation. Antiglycation activity was determined by measuring the formation of AGE fluorescence intensity, Nε-(carboxymethyl) lysine, and level of fructosamine. Protein oxidation was examined using levels of protein carbonyls and thiol group. Compounds significantly (p < 0.001) restricted the formation of fluorescent AGEs in fructose- BSA and methylglyoxal-BSA systems. Furthermore, there was a decrease in levels of fructosamine and protein carbonyls, and elevation in level of thiol group in fructose-BSA in presence of flavonoids. In summary, flavonoids from Polyalthia longifolia inhibit fructose-mediated protein glycation and oxidation, and can be potential agent for preventing AGE-mediated diabetic complications. [ABSTRACT FROM AUTHOR]

Dihydroxyacetone (DHA) is the only ingredient approved by the U.S. FDA as a colour additive in sunless tanning (self-tanning) products. Consumer sunless tanning products available for retail purchase contain 1–15% DHA. Although originally thought to only interact with the stratum corneum, more recent research has shown that DHA penetrates beyond the stratum corneum to living keratinocytes indicating a possible route of exposure in the epidermis. Normal Human Epidermal Keratinocytes (NHEK) were used to determine any potential in vitro toxicological effects of DHA in the epidermis. NHEK cells exposed to DHA concentrations up to 0.90% (100 mM) in dosing media were evaluated for viability, genotoxicity (Comet Assay), and gene expression changes by microarray analysis. Cell viability significantly decreased ∼50% after 3-h exposure to 50 and 100 mM DHA. DNA damage was only found to be significantly increased in cells exposed to cytotoxic DHA concentrations. A subtoxic dose of DHA induced significant gene expression changes. Particularly, expression of cyclin B1, CDK1, and six other genes associated with the G2/M cell cycle checkpoint was significantly decreased which correlates well with a G2/M block reported in the existing literature. Advanced Glycation End Product (AGE) formation significantly increased after 24 h of DHA exposure at and above 10 mM. In summary, these data show that DHA is cytotoxic above 25 mM in primary keratinocytes. Genotoxicity was detected only at cytotoxic concentrations, likely indicative of non-biologically relevant DNA damage, while subtoxic doses induce gene expression changes and glycation. DHA treatment had a significant and negative effect on primary keratinocytes consistent with in vitro cultured cell outcomes; however, more information is needed to draw conclusions about the biological effect of DHA in human skin. [ABSTRACT FROM AUTHOR]

Ultrasound-assisted extraction conditions were optimized to improve the extraction of advanced glycation end products (AGEs) inhibitors from Ecklonia cava extracts using response surface methodology. Conditions considered were extraction temperature (30–70°C), ethanol concentration (20–100%), and extraction time (10–50 min). Dependent variables were dieckol content, yield, and degree of AGEs inhibition measured in three anti-glycation assay models; namely, bovine serum albumin (BSA)-fructose (Fru), BSA-methylglyoxal (MGO), and BSA-glyoxal (GO). Overall, dieckol content increased, but AGEs formation and yield decreased, with increasing ethanol concentration. In the BSA-MGO model, AGEs inhibition decreased with increasing extraction temperature. The four-dimensional graphs were superimposed to select optimum conditions. The optimum conditions were determined as 50–60°C of extraction temperature, 70%–85% of ethanol concentration, and 25–35 min of extraction time. The suitability of the prediction model was evaluated by comparing the actual and predicted values of responses, and the results confirmed that our prediction model is suitable. IC50 of Ecklonia cava extract against BSA-Fru, BSA-MGO, and BSA-GO was 0.44, 0.56, and 0.73 mg/mL, respectively. The AGEs inhibition effect of Ecklonia cava extract in the BSA-MGO model was better than that of aminoguanidine at the same concentration. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) arising from dietary intake have been associated with numerous chronic diseases including cardiovascular diseases. The interaction between platelets and AGEs has been proposed to play a role in the etiology of cardiovascular diseases. However, the effects of the interaction between platelets and Maillard reaction products generated from glyoxal (Gly) or methylglyoxal (MG) are poorly understood. In this work, the effects of AGEs generated by the reaction between Gly or MG with Lys or bovine serum albumin (BSA) on platelet activation and aggregation were assessed. AGEs were generated incubating Gly or MG with Lys or BSA during 5 hours or 14 days, respectively. AGEs generation were characterized by kinetic studies and by amino acid analysis. Human platelet-rich plasma (PRP) was incubated with different concentrations of AGEs from Lys-MG or Lys-Gly and BSA-MG or BSA-Gly. Platelet activation was determined quantifying the expression of CD62 (P-selectin) in PRP exposed to different AGEs concentrations. It was found that Lys-MG and Lys-Gly induced an increase in P-selectin expression (p <.05), being 33.9% higher for Lys-MG when compared to Lys-Gly. Platelets incubated in the presence of BSA-MG and BSA-Gly did not show an increase in the P-selectin expression. Platelet aggregation was significantly higher for the mixture Lys-MG (in all the range of concentrations evaluated), whereas for Lys-Gly it was only significant the highest concentration (Lys 168 µM/Gly 168 µM). It was observed a significant increase in platelet aggregation induced by ADP for samples BSA-Gly. AGEs formed with MG-Lys induce a higher activation and aggregation of platelets when compared to those formed from Gly-Lys. [ABSTRACT FROM AUTHOR]

Glycation is a non-enzymatic biochemical reaction between reducing sugars and amino acids, causing the crosslinking and rearrangement of glycated proteins, leading to irreversible formation of Advanced Glycation End products (AGEs). Glycation is an activity that occurred both endogenously in our body and exposed to it through our diet as well, which contributed to the pool of AGEs and their pathology. AGEs played important role in various health conditions including and not limited to, hyperglycemia, inflammation, Alzheimer's disease, cardiovascular health and, ageing itself. While the formation of AGEs is irreversible, its formation can be inhibited or slowed down by natural products, which have anti-glycation activity. In this study, we explored the antiglycation activity of commercial herbal extracts of Artocarpus lakoocha and Pterocarpus marsupium using a competitive fluorescence assay. Both Artocarpus lakoocha and Pterocarpus marsupium extracts show highest anti-glycation activity (84.6–100%) after background correction, in a range of 10 to 100 mg/ml. [ABSTRACT FROM AUTHOR]

Purpose: Over the last two decades, increasing attention has been paid to environmental toxins and their effects on the female reproductive system. Endocrine disrupting chemicals (EDCs) are exogenous substances or mixtures that can mimic the action of steroid hormones and interfere with their metabolism. Advanced glycation end products (AGEs) are proinflammatory molecules that can interact with cell surface receptors and mediate the triggering of proinflammatory pathways and oxidative stress. The purpose of this review is to explore the effects of environmental toxin exposure in the pathogenesis of both polycystic ovary syndrome (PCOS) and OC (ovarian cancer), considered separately, and also to evaluate possible neoplastic ovarian repercussion after exposure in patients diagnosed with PCOS.Materials and methods: We searched PubMed for articles published in the English language with the use of the following MeSH search terms: "polycystic ovary syndrome" and "ovarian cancer" combined with "endocrine disruptors". Titles and abstracts were examined and full articles that met the selection criteria were retrieved. A manual search of review articles and cross-references completed the search.Results: Extensive data from different studies collected in recent years concerning the effects of EDC/AGE exposure have confirmed their role in the pathophysiology of both PCOS and OC. They favor PCOS/OC development through different mechanisms that finally lead to hormonal and metabolic disruption and epigenetic modifications.Conclusions: Environmental toxin exposure in PCOS women could favor neoplastic transformation by exacerbating and potentiating some PCOS features. Further research, although difficult, is needed in order to prevent further diffusion of these substances in the environment, or at least to provide adequate information to the population considered at risk. [ABSTRACT FROM AUTHOR]

All living organisms are normally undergoing aging. Dietary habits constitute the main environmental factor that may accelerate or decelerate this process. Advanced glycation end products (AGEs) are constituents of dietary products that are consumed daily, such as bread and milk. Although AGEs have been widely regarded as toxic agents, recent studies seem to contradict this view: they either find no adverse effects of AGEs or even attribute beneficial properties to them. The aim of our study was to investigate the effects of sugar-derived AGEs on organismal lifespan using as a model the nematode Caenorhabditis elegans. Exposure to sugar-derived AGEs prolonged the lifespan of wild type animals; this lifespan extension was accompanied by an enhanced pharyngeal pumping rate. We demonstrate that elevation of the pharyngeal pumping rate depends on W06A7.4 and eat-4 expression, as well as on daf-16, which encodes a FOXO family transcription factor. Our results suggest that sugar-derived AGEs modulate the lifespan of C. elegans at least in part through transcriptional regulation of pharyngeal pumping throughout the animals' lifespan. [ABSTRACT FROM AUTHOR]

Context:γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements. Objective:The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats. Materials and methods:GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 μM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs)in vitro. Forin vivoassessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed usingd-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina. Results:Our data showed that GLA inhibited the production of AGEs (IC50 = 1.12 ± 0.05 μM). However, this effect was more significant at lower tested doses. A similar pattern was also observed inin vivoexperiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). Thein silicodata exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE. Conclusion:The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline. [ABSTRACT FROM PUBLISHER]

Content:Recently, low-molecular-weight hyaluronic acid (LMWHA) has been reported to have novel features, such as free radical scavenging activities, antioxidant activities and dietary supplements. Objective:In this study, hyaluronic acid (HA) was extracted from rooster comb and LMWHA was obtained by ultrasonic degradation in order to assess their antioxidant and antiglycation activities. Materials and methods:Molecular weight (Mw) and the content of glucuronic acid (GlcA) were used as the index for comparison of the effect of ultrasonic treatment. The effects on the structure were determined by ultraviolet (UV) spectra and Fourier transform infrared spectra (FTIR). The antioxidant activity was determined by three analytical assays (DPPH, NO and TBARS), and the inhibitory effect against glycated-BSA was also assessed. Results:The GlcA content of HA and LMWHA was estimated at about 48.6% and 47.3%, respectively. The results demonstrate that ultrasonic irradiation decreases the Mw (1090–181 kDa) and intrinsic viscosity (1550–473 mL/g), which indicate the cleavage of the glycosidic bonds. The FTIR and UV spectra did not significantly change before and after degradation. The IC50value of HA and LWMHA was 1.43, 0.76 and 0.36 mg/mL and 1.20, 0.89 and 0.17 mg/mL toward DPPH, NO and TBARS, respectively. Likewise LMWHA exhibited significant inhibitory effects on the AGEs formation than HA. Discussion and conclusion:The results demonstrated that the ultrasonic irradiation did not damage and change the chemical structure of HA after degradation; furthermore, decreasing Mw and viscosity of LMWHA after degradation may enhance the antioxidant and antiglycation activity. [ABSTRACT FROM AUTHOR]

A diabetic vasculature is detrimental to cardiovascular health through the actions of advanced glycation end products (AGEs) on endothelial cells and platelets. Platelets activated by AGEs agonize endothelial responses promoting cardiovascular disease (CVD) development. While it has been established that AGEs can alter platelet functions, little is known about the specific platelet pathways that AGEs modify. Therefore, we evaluated the effects of AGEs on specific salient platelet pathways related to CVDs and whether the effects that AGEs elicit are dependent on glycation extent. To accomplish our objective, platelets were incubated with reversibly or irreversibly glycated albumin. A time course for adhesion and aggregation agonist receptor expression was assessed. Optical platelet aggregometry was used to confirm the functional activity of platelets after AGE exposure. In general, platelets subjected to glycated albumin had a significantly enhanced adhesion and aggregation potential. Furthermore, we observed an enhancement in dense body secretion and intracellular calcium concentration. This was especially prevalent for platelets exposed to irreversibly glycated albumin. Additionally, functional aggregation correlated well with receptor expression, suggesting that AGE-induced altered receptor sensitivity translated to altered platelet functions. Our findings indicate that under diabetic vascular conditions platelets become more susceptible to activation and aggregation due to an overall enhanced receptor expression, which may act to promote CVD development. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) formation is associated with different pathophysiological conditions, including diabetes mellitus. Our study aimed at screening the effect of 80 % aqueous methanol extract of leaves (AQME) of three commercial varieties ofMorus indica(G4, V1 and S36) and two wild varieties ofMorussp., (Morus laevigata- ML andMorus serrata-MS) onin vitroprotein glycation in BSA-glucose model. G4 exhibited the highest AGEs inhibition and metal ion chelation. It also inhibited cross-linking of protein glycation and protein aggregation. The G4 extract had a total polyphenol content of 96 mg GAE g-1and flavonoid content of 55.3 mg CE g-1. C-glycosyl flavonoids were identified and quantified in G4 by UPLC/MS. This is the first study reporting the presence of luteolin (258 μg g-1) and apigenin (164 μg g-1) in G4 variety which possess the most active anti-glycation property. Thus, G4 could be protective against hyperglycemia-mediated protein damage. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG) is generated from glycolytic metabolites, lipid peroxidation, glucose autooxidation and protein glycation. It is a prooxidant inducing oxidative stress and formation of advanced glycation end products (AGE). Effect of carnosine (CAR) as an antioxidant on toxicity due to MG has generated interest. In this study, rats were given incrementally increased doses (100–300 mg/kg) of MG in drinking water for ten weeks. CAR (250 mg/kg i.p.) was administered with MG. Plasma thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels were elevated by MG, and CAR decreased PC, AOPP and AGE levels. MG increased liver reactive oxygen species (ROS), TBARS, PC and AOPP levels, which were decreased by CAR. Thus,in vivorole of CAR on chronic MG administration was observed to suppress the generated hepatic and plasma oxidative stress. [ABSTRACT FROM AUTHOR]

Dilatation of the ascending aorta is a common occurrence in patients with bicuspid aortic valve (BAV). The aim of the current study was to characterize collagen content in advanced glycation end products (AGEs) of dilated aortic tissue from two distinct areas, concave and convex aortic sites in patients with BAV and TAV. Collagen contents extracted from 100 mg tissue was isolated by enzymatic digestion using pepsin and the nondigested material was further digested using cyanogen bromide, insoluble collagen fraction (ICF) was extracted by hydrochloric acid hydrolysis. BAV tissue showed diminished fluorescence of the pepsin extracted fraction (PEF) compared with TAV tissue (12.4 ± 1.0% vs 32.9 ± 7.6%,p = 0.05). Patients with BAV had PEF of collagens significantly diminished in the dilated ascending aorta, especially in its convex portion, in course of aging and increment of dilated diameters. It is suggestible that BAV patients present more highly AGE-modified collagens in their ascending aorta. [ABSTRACT FROM PUBLISHER]

Hyperglycemia and oxidative stress are involved in the development of diabetic nephropathy (DN). This study was designed to evaluate the effect of alcohol and hydroalcohol extract ofBacopa monnieriand stigmasterol isolated fromB. monnieriin the treatment of DN. Diabetes was induced in male wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. After 30 days, the rats were treated with different doses of extracts (100, 200, and 400 mg/kg) and stigmasterol (5 and 10 mg/kg) for 45 days to analyze their nephroprotective effect and produced significant attenuation in the serum glucose level, uric acid, creatinine, and lipid levels. Moreover, there is improvement in the level of superoxide dismutase (SOD), glutathione (GSH), and decrease in lipid peroxidation in terms of TBARS. The formation of AGEs in kidneys was also significantly reduced. These findings suggest thatB. monnieriand its isolate (stigmasterol) might inhibit the progression of DN. [ABSTRACT FROM AUTHOR]

Objective: To determine umbilical cord blood total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid-reacting substances (TBARS), advanced glycation end products (AGEs) and markers of oxidative stress in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and their associations with microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA), funisitis and selected aspects of short-term neonatal morbidity.Materials and Methods: One hundred and sixty-five women with singleton pregnancies complicated by PPROM were included in this study. Blood samples were obtained by venipuncture from the umbilical cord vein after the delivery of the newborn. The umbilical cord blood concentrations of TAC, FRAP, TBARS and AGEs were measured.Results: The presence of MIAC, HCA and funisitis did not show differences in the umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations. Positive correlations were found between the gestational age at sampling and umbilical cord blood TAC and AGEs concentrations (TAC: rho = 0.26; p = 0.001; AGEs: rho = 0.35; p < 0.0001). There was no association between umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations and selected aspects of short-term neonatal morbidity.Conclusions: Oxidative stress is associated with PPROM, as indicated by the presence of markers tested in the umbilical cord blood; however, the evaluated oxidative stress markers are not influenced by the presence of MIAC and/or HCA, and funisitis or subsequent development of selected aspects of short-term neonatal morbidity. [ABSTRACT FROM AUTHOR]

Introduction In recent years, the role of high mobility group box-(HMGB-1) protein and its receptors has received increasing attention. It has been documented that HMGB-1 is associated with disease activity in systemic lupus erythematosus (SLE). HMGB-1 supports the inflammatory clearance of apoptotic cells and remnants. It binds to molecules released from apoptotic cells such as nucleosomes and DNA thereby, increasing the immunogenicity of macrophages through receptors for advanced glycation end products (sRAGE). Aim of the work Was to measure the plasma level of sRAGE in SLE patients and to correlate it with the clinical and laboratory parameters of disease activity. Patients and methods The study was composed of 35 SLE patients; 31 females and 4 males (Group I) and 20 age and gender matched healthy subjects as a control (Group II). All patients fulfilling the American College of Rheumatology (ACR) classification criteria for the diagnosis of SLE. Active disease was identified using SLE disease activity index (SLE-DAI). Demographic data, cutaneous manifestations, arthritis, vasculitis, myositis, renal, and hematological disorders were recorded. In addition; complete blood picture, blood urea, serum creatinine, 24 h urine proteins, creatinine clearance, protein/creatinine ratio, C3, C4, Anti-nuclear antibody, Anti-double stranded DNA were conducted for all patients and controls. Results The mean value of plasma level of (sRAGE) in SLE patients was significantly higher in SLE patients than in the normal healthy controls ( P < 0.001). There was a statistically significant positive correlation between sRAGE and SLE-DAI ( P < 0.001). Conclusion The plasma level of sRAGE is considered as a potential biomarker for disease activity in SLE, severity and prognosis. [ABSTRACT FROM AUTHOR]

Effect of aqueous methanol extract of different colour sweet bell peppers (Capsicum annuumL.) on parameters of diabesity and carbonyl stress was analysedin vitro. Yellow pepper displayed significantly (p < 0.001) higher intestinal α-glucosidase inhibitory activity than green and red pepper. Porcine pancreatic lipase inhibitory activity was significantly (p < 0.01) high in yellow and red pepper than in green pepper. Green and red pepper inhibited vesperlysine-type advanced glycation end products (AGEs) more potently than yellow pepper; however, pentosidine-type AGEs were similarly inhibited by all three peppers. Yellow and red pepper inhibited lipid peroxidation more potently (p < 0.01) than green pepper. Total polyphenol content and free radicals scavenging activities in yellow and red bell peppers were higher than in green pepper. Total flavonoid content was high in green pepper than that present in yellow and red peppers. Green pepper displayed presence of proanthocyanins; however, oligomeric anthocyanins were detected in yellow and red peppers. [ABSTRACT FROM PUBLISHER]

Context: During diabetes mellitus, non-enzymatic reaction between amino groups of protein and carbonyl of reducing sugars (Millard reaction) is responsible for the major diabetic complications. Various efforts have been made to influence the process of protein glycation. Objectives: This review article provides an extensive survey of various studies published in scientific literature to understand the process of protein glycation and its measurement. Moreover, evaluation and identification of potential inhibitors (antiglycation agents) of protein glycation from natural and synthetic sources and their mechanism of actionin vitroandin vivoare also addressed. Method: In this review article, the mechanism involved in the formation of advanced glycation end products (AGEs) is discussed, while in second and third parts, promising antiglycation agents of natural and synthetic sources have been reviewed, respectively. Finally,in vivostudies have been addressed. This review is mainly compiled from important databases such as Science, Direct, Chemical Abstracts, SciFinder, and PubMed. Results: During the last two decades, various attempts have been made to inhibit the process of protein glycation. New potent inhibitors of protein glycation belonging to different classes such as flavonoids, alkaloids, terpenes, benzenediol Schiff bases, substituted indol, and thio compounds have been identified. Conclusion: Antiglycation therapy will be an effective strategy in future to prevent the formation of AGEs for the management of late diabetic complications Current review article highlighted various compounds of natural and synthetic origins identified previously to inhibit the protein glycation and formation of AGEsin vitroandin vivo. [ABSTRACT FROM PUBLISHER]

The antiglycative effect of γ-glutamyl-S-allyl-cysteine (GSAC) peptide isolated from fresh garlic scales was investigated in the bovine serum albumin (BSA)/glucose system. GSAC inhibited the increase of fluorescence intensity at about 440 nm in a concentration-dependent manner and reduced reacted free lysine side chains by 10.9%, 24.7% and 37.7%, as the GSAC concentrations increased from 0.1 to 2.5 mg mL− 1. Glycation-specific decline in BSA α-helix content (from 61.3% to 55.6%) and increase in β-sheet (from 2.1% to 5.4%) were prevented by GSAC (2.5 mg mL− 1)in vitro, implying its stabilisation effect. GSAC treatment (2.5 mg mL− 1) suppressed protein crosslinking to form polymers. Additionally, GSAC (10, 40, and 160 μg mL− 1) showed radical-scavenging and metal-chelating capacities. In conclusion, GSAC has an antiglycative effect, which may involve its radical-scavenging and metal-chelating capacities. [ABSTRACT FROM PUBLISHER]

Background: Advanced glycation end products (AGEs) have biological properties that may contribute to the mortality of children on hemodialysis (HD). This study examines the relationship of LMW fluorescence AGEs, oxidized LDL (ox-LDL), soluble receptor AGE (sRAGE) as markers of oxidative stress in children with end stage renal disease (ESRD) undergoing HD.Method: Thirty children with ESRD undergoing HD, and 30 healthy, age- and sex-matched children were included. Serum levels of LMW fluorescence AGEs, sRAGE, oxidized LDL (ox-LDL), pre- and post-dialysis urea, high-sensitivity C-reactive protein (hs-CRP), hemoglobin (Hb) and serum albumin (ALB), were measured.Results: Abnormal serum inflammatory changes: elevated levels of LMW AGEs, sRAGE, oxLDL, CRP and urea were exhibited in HD children compared with healthy controls; more so in anemic when compared to non-anemic patients. Significant positive correlation was found between serum levels of AGEs and sRAGE.Conclusion: The low molecular weight form of AGEs is associated with oxidative stress in children receiving chronic HD, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients. LMW AGEs levels showed a negative correlation with sRAGE and both exhibit a significant negative relation to seum urea. [ABSTRACT FROM PUBLISHER]

Purpose: To evaluate the relationship between skin autofluorescence (SAF), which reflects the accumulation of advanced glycation end products (AGEs), and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes. Methods: Sixty-seven eyes of 67 patients with type 2 diabetes were enrolled. Sixty-seven age-matched non-diabetic subjects served as controls. Diabetic patients were classified by the severity of their DR: no DR (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). SAF was measured with an autofluorescence reader. Results: SAF in the diabetes patients was significantly higher than in the controls (median 2.5 (interquartile range 2.3-2.7) and 1.8 (1.6-2.3) arbitrary unit (AU), respectively, p < 0.001). There was a statistically significant increase in SAF along with the increasing severity of DR (from NDR to NPDR: p = 0.034; NPDR to PDR: p < 0.01). Logistic regression analysis revealed that SAF (OR, 17.2; p < 0.05) was an independent factor indicating the presence of PDR. Conclusions: SAF has an independent relationship with PDR in patients with type 2 diabetes. SAF measurement with an autofluorescence reader is a non-invasive way to assess the risk of DR. SAF may, therefore, be a surrogate marker candidate for the non-invasive evaluation of DR. [ABSTRACT FROM AUTHOR]

Background: An increasing number of studies have demonstrated of that diabetes mellitus (DM) is associated with an increased prevalence of Alzheimer disease (AD), the underlying mechanisms are still obscure. Methods: We developed a streptozotocin (STZ)-induced diabetic AD transgenic mouse model and evaluated the effect of hyperglycemia on senile plaque formation. Results: Our data showed that administration of STZ increased the level of blood glucose and increased the advanced glycation end products (AGEs) in brain tissue, and further enhanced the expression levels of the receptor for AGEs (RAGE) and the nuclear factor-kappa B (NF-κB) in the brain, and accelerated the senile plaque formation in the transgenic mice. Our results showed that STZ-induced insulin-deficient hyperglycemia caused the pathophysiology of AD in APP/PS1 transgenic mice by modulating the AGEs/RAGE/NF-κB pathway. Conclusions: Our study suggests that there is a close linkage of DM and cerebral amyloidosis in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are stable end products of the Maillard reaction. Effects of food extracts are often initially analysed in cellular test systems and it is not clear how different cell culture conditions might influence the results. Therefore, we compared the effects of two models for AGE-rich food, bread crust and coffee extract (CE) on WI-38 human lung fibroblasts under different cell culture conditions (sub-confluent versus confluent cells, with and without serum). WI-38 cells responded to coffee and bread crust extract (BCE) with a rapid phosphorylation of PKB (AKT), p42/44 MAPK (ERK 1/2) and p38 MAPK, strongly depending on culture conditions. BCE resulted in increased cell numbers, whereas CE appeared to be cytotoxic. When cell numbers under all culture conditions and treatments were correlated with kinase phosphorylation, the relation between phospho-p38 MAPK and phospho-AKT represented a good, cell culture condition-independent predictor of cell survival. [ABSTRACT FROM AUTHOR]

Elevated levels of pro-oxidants and various markers of oxidative tissue damage were found in diabetic patients, indicating involvement of oxidative stress in the pathogenesis of diabetes mellitus (DM). On one side, physiological levels of reactive oxygen species (ROS) play an important role in redox signaling of various cells, while on the other, excessive ROS production can jeopardize the integrity and physiological functions of cellular macromolecules, in particular proteins, thus contributing to the pathogenesis of DM. Reactive aldehydes, especially 4-hydroxynonenal (HNE), are considered as second messengers of free radicals that act both as signaling molecules and as cytotoxic products of lipid peroxidation causing long-lasting biological consequences, in particular by covalent modification of macromolecules. Accordingly, the HNE and related reactive aldehydes may play important roles in the pathophysiology of DM, both in the development of the disease and in its progression and complications due to the following: (i) exposure of cells to supraphysiological levels of 4-hydroxyalkenals, (ii) persistent and sustained generation of 4-hydroxyalkenals that progressively affect vulnerable cells that lack an efficient bioactive aldehyde neutralization system, (iii) altered redox signaling influenced by reactive aldehydes, in particular by HNE, and (iv) induction of extracellular generation of similar aldehydes under secondary pathological conditions, such as low-grade inflammation. [ABSTRACT FROM AUTHOR]

Glycation of proteins or other biomolecules and their further long-term degradation result in the formation of advanced glycation end products, AGEs. AGEs and other ligands interact with their receptors, RAGEs, localized to a variety of tissues, but mainly in endothelium and vascular wall cells. This interaction triggers diverse signaling pathways that converge on the activation of NF-κB and the initiation of a local inflammatory reaction that, when prolonged, results in dysfunctional features. Preeclampsia is a serious vascular disorder centred at the placenta-uterine interface, the placental bed, but the condition extends to the mother´s circulation. RAGEs have notorious expression in the placental bed tissues along pregnancy but, in addition, RAGEs and their ligands are expressed in the fetal membranes and are found in the amniotic fluid and the mother´s serum. Disorders complicating pregnancies and having an important vascular involvement, as preeclampsia and diabetes mellitus, have additional enhanced AGE/RAGE expression variation. This indicates that for their assessment, the assay of RAGEs or their ligands may become useful diagnostic or prognostic procedures. [ABSTRACT FROM AUTHOR]

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation. [ABSTRACT FROM AUTHOR]

Objective: To study a recombined chimeric peptide consisting of lysozyme N-terminal sequence and exendin-4 (shortly LYZ(N)-EX4) as a dual-action peptide for diabetes. Methods: LYZ( N) -EX4 was recombined into plasmid pET-32a( +) and expressed in Escherichia coli. The fusion protein was separated by affinity chromatography and hydrolyzed by enterokinase to prepare LYZ(N)-EX4. The chimeric peptide was digested by thrombin and the digests were analyzed by HPLC. The secondary peptides were identified by mass spectrometry. Biological activities of the thrombin digests were determined in vitro, using NIT-1 cells for insulin promoting action and using human white blood cells (WBC) for anti-AGEs action. Results: The fusion protein was highly expressed in E. coli and LYZ(N)-EX4 was obtained via hydrolysis of the fusion protein. The thrombin digests of LYZ(N)-EX4 were separated by HPLC into two peaks, which were identified as LYZ(N) and EX4 by mass spectrametry. Functional studies found that the digests were able to antagonize the effects of AGEs on expression of RAGE mRNA in WBC, promote cell activity, stimulate PDX-1 mRNA expression and increase insulin secretion by NIT-1 cells, suggesting the actions of LYZ(N) and EX4 on the cells. Conclusions: LYZ(N)-EX4 was sensitive to thrombin digestion, and the secondary peptides LYZ(N) and EX4 could function as anti-AGEs and insulin-promoting peptides, respectively. [ABSTRACT FROM AUTHOR]

Antiglycating potentials ofDerris indicaL., derived constituents were evaluated against advanced glycation end product formation using in vitro bioassays and compared with those of commonly used standards. The structures of 12 constituents ofDerris indicawere characterized by spectroscopic analyses (NMR and Mass). Further, these constituents were simultaneously determined using high performance liquid chromatography (HPLC) using a Waters XTerra RP18 column (250 × 4.6 mm, 5 µ) with a gradient elution system comprising of acetonitrile, water and 0.1% (v/v) acetic acid, flow rate 0.8 mL/min and column temperature 25°C, respectively. The limits of detection (LODs) were below 0.10 µg/mL, whereas the limits of quantification (LOQs) were below 0.30 µg/mL. It is concluded that the method has merits such as high sensitivity, specificity, and simplicity versus those of the other methods reported in the literature. [ABSTRACT FROM AUTHOR]

Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. They have been etiologically implicated in numerous diabetes- and age-related diseases. Strategies inhibiting AGE accumulation and signaling seem to possess a therapeutic potential in these pathologies. However, still little is known on the precise role of AGEs during skin aging. In this review the existing literature on AGEs and skin aging will be reviewed. In addition, existing and potential anti-AGE strategies that may be beneficial on skin aging will be discussed. [ABSTRACT FROM AUTHOR]

The individual phenolic acids, total phenolic content, total flavonoid content and antioxidant activity of azuki bean (Vigna angularis) varieties from 13 provinces of China were investigated. Eight phenolic compounds were analysed on an ultra-performance liquid chromatography-mass spectrometry system. The results obtained suggest that the azuki beans can be considered as a good source of phenolic compounds, and growing the azuki beans at high altitude may be an effective way to enhance the antioxidant and antidiabetic potential of the beans. [ABSTRACT FROM AUTHOR]

Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction. [ABSTRACT FROM PUBLISHER]

Background: Advanced glycation end product (AGE) levels are elevated in patients with decreased renal function and may contribute to the excessive cardiovascular disease in this population. However, their relation to nutrition, anemia, and micro inflammation is not well characterized. The aim of this study is to determine their relationship in patients with chronic kidney disease (CKD). Methods: The studied group consisted of 203 subjects: 159 patients with CKD 1--5 and 44 healthy control subjects. AGE levels were assessed by spectrofluorimetry, and routine biochemical parameters were measured using standard methods. Results: AGE levels were significantly increased in CKD patients compared with controls (3.9 ±± 1.7 ×× 105 AU in CKD 1--5 patients vs. 3.2 ±± 0.48 ×× 105 AU in controls, p < 0.0001). AGE levels increased from CKD 3. AGE levels were positively associated with age, albumin, prealbumin, and orosomucoid, and were negatively associated with hemoglobin and estimated glomerular filtration rate. In multiple regression analysis, after adjustment to age and glomerular filtration rate, AGE levels remained independently correlated with albumin and prealbumin and negatively correlated with hemoglobin. Conclusions: This study is the demonstration that nutrition markers, albumin and prealbumin, are the positive determinants and hemoglobin is the negative determinant of serum AGE levels in patients with CKD. [ABSTRACT FROM AUTHOR]

Oxidized and cross-linked modified proteins are known to accumulate in ageing. Little is known about whether the accumulation of proteins modified by advanced glycation end products (AGEs) is due to an affected intracellular degradation. Therefore, this study was designed to determine whether the intracellular enzymes cathepsin B, cathepsin D and the 20S proteasome are able to degrade AGE-modified proteins in vitro. It shows that AGE-modified albumin is degraded by cathepsin D, while cathepsin B was less effective in the degradation of aldehyde-modified albumin and the 20S proteasome was completely unable to degrade them. Mouse primary embryonic fibroblasts isolated from a cathepsin D knockout animals were found to have an extensive intracellular AGE-accumulation, mainly in lysosomes, and a reduction of AGE-modified protein degradation compared to cells isolated from wild type animals. In summary, it can be assumed that cathepsin D plays a significant role in the removal of AGE-modified proteins. [ABSTRACT FROM AUTHOR]

Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) termed advanced glycation end products (AGEs) are known to be produced by nonenzymatic glycation between bovine serum albumin (BSA) and D-glucose. This study is to characterize the immunoreactivity of anti-AGE antibodies including anti-CML and anti-CEL antibodies. Using AGE-modified BSA (AGE-BSA) as an immunogen, a polyclonal anti-AGE immunoglobulin G (IgG) was produced. The anti-AGE IgG could strongly detect AGEs formed on BSA, at least in part, AGEs produced on both residues Lys and Arg due to its immunoreaction with Lys-derived and Arg-derived AGEs produced by NaCNBH3, a reducing agent, in amino acid glycation analysis, but the pre-immune serum could not. As the anti-CML antibody could also strongly react with AGE-BSA, this suggests that CML is a major nonenzymatically glycated product cross-linked to BSA. Furthermore, CEL is associated with distinguishable polymerization of BSA from CML polymerization of BSA, though weaker than CML and was not produced by Lys glycation analysis. These results indicate that the anti-AGE antibody is effective for detecting both Lys-derived and Arg-derived AGEs, and CML and CEL distinctively polymerize albumin as major AGEs present on AGE-BSA. [ABSTRACT FROM AUTHOR]