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1.
A systematic review of antiglycation medicinal plants.
Asgharpour Dil, F, Ranjkesh, Z, Goodarzi, MT
Diabetes & metabolic syndrome. 2019;(2):1225-1229
Abstract
BACKGROUND AND OBJECTIVES The present review shows a list of anti-glycation plants with their anti-glycation activity mechanisms that can attract the attention of pharmacologist for further scientific research towards finding better remedy for diabetic complications. MATERIALS Google scholar, Pubmed, Web of Science and Scopus were searched. The terms were advanced glycation end products (AGEs), medicinal plants, antiglycation products. RESULTS plants that studied in this review inhibit glycation in several possible mechanisms. Some of these plants inhibit the production of shiff base and amadori products. The others inhibit the generation of amadori products in the advanced phase. Some others blocked the aggregation of AGEs and some plants have antioxidant activity and reduce AGEs formation by preventing oxidation of amadori product and metal-catalyzed glucoxidation. CONCLUSION This review can help pharmacologist to find antiglycation natural substance that can be useful in treatment of diabetic complications.
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Gradual increase in advanced glycation end-products from no diabetes to early and regular gestational diabetes: A case-control study.
Cosson, E, Gary, F, Nguyen, MT, Bianchi, L, Sandre-Banon, D, Biri, L, Jaber, Y, Cussac-Pillegand, C, Banu, I, Chiheb, S, et al
Diabetes & metabolism. 2019;(6):586-589
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The Relevance of Toxic AGEs (TAGE) Cytotoxicity to NASH Pathogenesis: A Mini-Review.
Sakasai-Sakai, A, Takata, T, Takino, JI, Takeuchi, M
Nutrients. 2019;(2)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is associated with an increased prevalence of fatty liver. Under hyperglycemic conditions, advanced glycation end-products (AGEs) are generated through a non-enzymatic glycation reaction between the ketone or aldehyde groups of sugars and amino groups of proteins. Glyceraldehyde (GA) is a metabolic intermediate of sugars, and GA-derived AGEs (known as toxic AGEs (TAGE)) have been implicated in the development of NASH. TAGE accumulates more in serum or liver tissue in NASH patients than in healthy controls or patients with simple steatosis. Furthermore, the TAGE precursor, GA, causes cell damage through protein dysfunctions by TAGE modifications and induces necrotic-type hepatocyte death. Intracellular TAGE may leak outside of necrotic-type cells. Extracellular TAGE then induce inflammatory or fibrotic responses related to the pathology of NASH in surrounding cells, including hepatocytes and hepatic stellate cells. This review focuses on the contribution of TAGE to the pathology of NASH, particularly hepatic cell death related to NASH.
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Skin Autofluorescence Measurement in Subclinical Atheromatous Disease: Results from the ILERVAS Project.
Sánchez, E, Betriu, À, Yeramian, A, Fernández, E, Purroy, F, Sánchez-de-la-Torre, M, Pamplona, R, Miquel, E, Kerkeni, M, Hernández, C, et al
Journal of atherosclerosis and thrombosis. 2019;(10):879-889
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Abstract
AIM: Advanced glycation end-products (AGEs) have been involved in the atherogenic process in the high-risk population. The goal of this study was to demonstrate that AGEs are related to subclinical atheromatous disease in subjects with low to moderate vascular risk. METHODS A cross-sectional study in which 2,568 non-diabetic subjects of both sexes without cardiovascular disease were included. Subcutaneous content of AGEs was assessed by skin autofluorescence (SAF) and subclinical atheromatous disease was measured by assessing the atheromatous plaque burden in carotid and femoral regions using ultrasonography. In addition, serum pentosidine, carboxymethyl-lysine (CML) and AGE receptors (RAGE) were assessed in a nested case-control study with 41 subjects without plaque and 41 individuals subjects with generalized disease. RESULTS Patients with atheromatous plaque had a higher SAF than those with no plaque (1.9 [1.7 to 2.3] vs. 1.8 [1.6 to 2.1] arbitrary units (AU), p<0.001). The SAF correlated with the total number of affected regions (r= 0.171, p<0.001), increasing progressively from 1.8 [1.6 to 2.1] AU in those without atheromatous disease to 2.3 [1.9 to 2.7] AU in patients with ≥ 8 plaques (p<0.001). A correlation was also observed between SAF and the total plaque area (r=0.113, p<0.001). The area under the Receiver Operating Characteristic curve was 0.65 (0.61 to 0.68) for identifying male subjects with atheromatous disease. The multivariable logistic regression model showed a significant and independent association between SAF and the presence of atheromatous disease. However, no significant differences in serum pentosidine, CML, and RAGE were observed. CONCLUSIONS Increased subcutaneous content of AGEs is associated with augmented atheromatous plaque burden. Our results suggest that SAF may provide clinically relevant information to the current strategies for the evaluation of cardiovascular risk, especially among the male population.
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Development and Progression of Non-Alcoholic Fatty Liver Disease: The Role of Advanced Glycation End Products.
Fernando, DH, Forbes, JM, Angus, PW, Herath, CB
International journal of molecular sciences. 2019;(20)
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the adult population and is now a major cause of liver disease-related premature illness and deaths in the world. Treatment is largely based on lifestyle modification, which is difficult to achieve in most patients. Progression of simple fatty liver or steatosis to its severe form non-alcoholic steatohepatitis (NASH) and liver fibrosis has been explained by a 'two-hit hypothesis'. Whilst simple steatosis is considered the first hit, its transformation to NASH may be driven by a second hit. Of several factors that constitute the second hit, advanced glycation end products (AGEs), which are formed when reducing-sugars react with proteins or lipids, have been implicated as major candidates that drive steatosis to NASH via the receptor for AGEs (RAGE). Both endogenous and processed food-derived (exogenous) AGEs can activate RAGE, mainly present on Kupffer cells and hepatic stellate cells, thus propagating NAFLD progression. This review focuses on the pathophysiology of NAFLD with special emphasis on the role of food-derived AGEs in NAFLD progression to NASH and liver fibrosis. Moreover, the effect of dietary manipulation to reduce AGE content in food or the therapies targeting AGE/RAGE pathway on disease progression is also discussed.
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Dietary Fiber Intake: Its Relation With Glycation End Products and Arterial Stiffness in End-Stage Renal Disease Patients.
Demirci, BG, Tutal, E, Eminsoy, IO, Kulah, E, Sezer, S
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2019;(2):136-142
Abstract
OBJECTIVE We aimed to analyze the relationship between the effect of total dietary fiber intake on C-reactive protein (CRP) and on oxidative stress parameters such as serum advanced glycation end products (AGEs), superoxide dysmutase (SOD), malondialdehyde, and arterial stiffness by pulse wave velocity (PWv) in maintanace hemodialysis (MHD) patients. METHODS Among 650 MHD patients, 128 were selected according to inclusion criteria. The dietary survey was performed with a 3-day dietary history. Dietary fiber level was adjusted for total energy intake by the residual method. Patients were stratified by quartiles of adjusted dietary fiber (ADF) level as group 1 (n = 32) (ADF: <8.86 g/day), group 2 (n = 35) (ADF: 8.86-12.50 g/day), group 3 (n = 31) (ADF: 12.51-15.90 g/day), and group 4 (n = 30) (ADF: ≥15.91 g/day). Monthly assessed biochemical parameters including serum hemoglobin, albumin, CRP, calcium, phosphorus, and lipid profile levels were recorded. Serum AGEs, SOD, and malondialdehyde levels were determined by ELISA method. The PWv was determined from pressure tracing over carotid and femoral arteries. RESULTS Patients in group 3 and 4 had significantly lower CRP and AGE than those in group 1 and 2. Mean serum SOD level and PWv were significantly higher in group 4. In regression analysis, ADF intake was the unique predictor for both AGE (r2 = 0.164, P = 0.017) and CRP levels (r2 = 0.238, P = 0.01). CONCLUSION Present data show that dietary fiber intake is independently correlated with inflammation and oxidative stress. In addition, decreased fiber intake results in impaired arterial stiffness. Thus, adequate fiber intake could prevent cardiovascular events and inflammatory processes in patients undergoing MHD.
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Experimental Hyperglycemia Alters Circulating Concentrations and Renal Clearance of Oxidative and Advanced Glycation End Products in Healthy Obese Humans.
Perkins, RK, Miranda, ER, Karstoft, K, Beisswenger, PJ, Solomon, TPJ, Haus, JM
Nutrients. 2019;(3)
Abstract
The purpose of this investigation was to evaluate the effects of experimental hyperglycemia on oxidative damage (OX), advanced glycation end products (AGEs), and the receptor for AGEs (RAGE) through an in vivo approach. Obese subjects (n = 10; 31.2 ± 1.2 kg·m-2; 56 ± 3 years) underwent 24 h of hyperglycemic clamp (+5.4 mM above basal), where plasma at basal and after 2 h and 24 h of hyperglycemic challenge were assayed for OX (methionine sulfoxide, MetSO, and aminoadipic acid, AAA) and AGE-free adducts (Ne-carboxymethyllysine, CML; Ne-carboxyethyllysine, CEL; glyoxal hydroimidazolone-1, GH-1; methylglyoxal hydroimidazolone-1, MG-H1; and 3-deoxyglucosone hydroimidazolone, 3DG-H) via liquid chromatography⁻tandem mass spectrometry (LC⁻MS/MS). Urine was also analyzed at basal and after 24 h for OX and AGE-free adducts and plasma soluble RAGE (sRAGE) isoforms (endogenous secretory RAGE, esRAGE, and cleaved RAGE, cRAGE), and inflammatory markers were determined via enzyme-linked immunosorbent assay (ELISA). Skeletal muscle tissue collected via biopsy was probed at basal, 2 h, and 24 h for RAGE and OST48 protein expression. Plasma MetSO, AAA, CEL, MG-H1, and G-H1 decreased (-18% to -47%; p < 0.05), while CML increased (72% at 24 h; p < 0.05) and 3DG-H remained unchanged (p > 0.05) with the hyperglycemic challenge. Renal clearance of MetSO, AAA, and G-H1 increased (599% to 1077%; p < 0.05), CML decreased (-30%; p < 0.05), and 3DG-H, CEL, and MG-H1 remained unchanged (p > 0.05). Fractional excretion of MetSO, AAA, CEL, G-H1, and MG-H1 increased (5.8% to 532%; p < 0.05) and CML and 3DG-H remained unchanged (p > 0.05). Muscle RAGE and OST48 expression, plasma sRAGE, IL-1β, IL-1Ra, and TNFα remained unchanged (p > 0.05), while IL-6 increased (159% vs. basal; p > 0.05). These findings suggest that individuals who are obese but otherwise healthy have the capacity to prevent accumulation of OX and AGEs during metabolic stress by increasing fractional excretion and renal clearance.
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Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study.
Martens, RJH, Broers, NJH, Canaud, B, Christiaans, MHL, Cornelis, T, Gauly, A, Hermans, MMH, Konings, CJAM, van der Sande, FM, Scheijen, JLJM, et al
PloS one. 2019;(8):e0221058
Abstract
BACKGROUND Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. METHODS We examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. RESULTS After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. CONCLUSIONS In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.
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Influence of the Maillard Reaction on the Allergenicity of Food Proteins and the Development of Allergic Inflammation.
Toda, M, Hellwig, M, Henle, T, Vieths, S
Current allergy and asthma reports. 2019;(1):4
Abstract
PURPOSE OF REVIEW The Maillard reaction (MR) is a non-enzymatic reaction between reducing sugars and compounds with free amino groups such as proteins and takes place during thermal processing and storage of foods. This review aims to discuss potential effects of dietary MR products on the pathological mechanisms of allergic diseases. RECENT FINDINGS Since the MR leads to modification of proteins with various types of glycation structures, the impact of the MR on the immunogenicity and potential allergenicity of food proteins in many allergenic foods has been assessed. In addition, recent studies have suggested that the MR products, in particular "advanced glycation end products (AGEs)," contained in the diet may be involved in the development of chronic inflammation by acting as inflammatory components and affecting the gut microbiome. This review found that the biological, immunological, and allergic properties of dietary MR products are diverse due to the complexity of the MR.
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Effect of reducing dietary advanced glycation end products on obesity-associated complications: a systematic review.
Ribeiro, PVM, Tavares, JF, Costa, MAC, Mattar, JB, Alfenas, RCG
Nutrition reviews. 2019;(10):725-734
Abstract
CONTEXT Consumption of dietary advanced glycation end products (AGEs) is associated with oxidative stress, inflammation, and other chronic conditions commonly associated with obesity. OBJECTIVE To analyze the effects of dietary AGEs on complications associated with obesity. DATA SOURCES This systematic review was conducted and reported according to PRISMA guidelines. The PubMed, Cochrane, and Scopus databases were searched, using the terms "advanced glycation end products," "overweight," and "obesity." The last search was performed in October 2018. DATA EXTRACTION Six studies that evaluated the effects of low-AGE and high-AGE diets were included in the review. The duration of the studies ranged from 1 day to 12 weeks. A comparison of all the compiled data was conducted by the authors. DATA ANALYSIS Circulating and urinary AGE markers, besides soluble receptor for AGEs, were considered as the primary outcomes. The secondary outcomes were cardiometabolic, inflammatory, glycemic, anthropometric, and renal markers. CONCLUSIONS AGE-RAGE interactions can activate the NF-κB (nuclear factor kappa B) signaling pathway and inhibit the PI3K-AKT pathway in adipocytes, which may explain their association with chronic diseases. This interaction can be considered as a novel explanation for the pathogenesis of obesity. AGEs can also be used as a biomarker for monitoring responses to dietary interventions in overweight and obese people. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42018082745.