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, Remy J H; Broers, Natascha J. H.; Canaud, Bernard; Christiaans, Maarten H. L.; Cornelis, T.; Gauly, Adelheid; Hermans, Marc; Konings, Constantijn; Sande, Frank M. van der; Scheijen, Jean L.J.M.; Stifft, Frank; Wirtz, Joris J. J. M.; Kooman, Jeroen P.; Schalkwijk, Casper G.

doi:10.1371/journal.pone.0221058

Cited by 24 publications

(32 citation statements)

References 55 publications

(66 reference statements)

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“…It has been described that the plasma concentration in type 2 diabetes patients of 3-DG is 1.37 μ mol/L, of GO 0.74 μ mol/L, and of MGO 0.31 μ mol/L [ 54 ]. In serum of patients with chronic kidney disease, the amounts have been found to be of 1.64 μ mol/L for 3-DG, 1.72 μ mol/L for GO, and 1.08 μ mol/L for MGO [ 55 ]. In peritoneal dialysis fluids, 3-DGal has been detected at a concentration of ≤16 μ mol/L and 3-DG at a concentration of ≤7 μ mol/L [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet‐Related Advanced Glycation End Products and Related 1,2‐Dicarbonyls

Cepas

Manig

Mayo

et al. 2021

Oxidative Medicine and Cellular Longevity

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During food processing and storage, and in tissues and fluids under physiological conditions, the Maillard reaction occurs. During this reaction, reactive 1,2-dicarbonyl compounds arise as intermediates that undergo further reactions to form advanced glycation end products (AGEs). Diet is the primary source of exogenous AGEs. Endogenously formed AGEs have been proposed as a risk factor in the pathogenesis of diet-related diseases such as diabetes, insulin resistance, cardiovascular diseases, or chronic disease. AGEs may differently contribute to the diet-related exacerbation of oxidative stress, inflammation, and protein modifications. Here, to understand the contribution of each compound, we tested individually, for the first time, the effect of five 1,2-dicarbonyl compounds 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal (GO), and methylglyoxal (MGO) and four different glycated amino acids N-ε-(carboxyethyl)lysine (CEL), N- ε -(carboxymethyl)lysine (CML), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pyrraline (Pyrr) in a cell line of human keratinocytes (HaCaT). We found that most of the glycated amino acids, i.e., CEL, CML, and MG-H1, did not show any cytotoxicity. At the same time, 1,2-dicarbonyl compounds 3-DGal, 3,4-DGE, GO, and MGO increased the production of reactive oxygen species and induced cell death. MGO induced cell death by apoptosis, whereas 3-DGal and 3,4-DGE induced nuclear translocation of the proinflammatory NF-κB transcription pathway, and the activation of the pyroptosis-related NLRP3 inflammasome cascade. Overall, these results demonstrate the higher toxic impact of 1,2-dicarbonyl compounds on mucosal epithelial cells when compared to glycated amino acids and the selective activation of intracellular signaling pathways involved in the crosstalk mechanisms linking oxidative stress to excessive inflammation.

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Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet‐Related Advanced Glycation End Products and Related 1,2‐Dicarbonyls

Cepas

Manig

Mayo

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Also, we found a notable presence of MG-H1 in the epidermis, which may partly explain this finding. Moreover, previous studies in different body compartments (serum and lens proteins) have shown mixed results [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Is skin autofluorescence (SAF) representative of dermal advanced glycation endproducts (AGEs) in dark skin? A pilot study

Atzeni

Boersema

Pas

et al. 2020

Heliyon

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“…Advanced glycation end products (AGEs), proinflammatory and pro-oxidative compounds classified as uremic toxins, are produced through the non-enzymatic glycation and oxidation of proteins, lipids, and nucleic acids. Their accumulation in CKD promotes endothelial dysfunction and subsequent diseases [ 115 , 116 , 117 , 118 , 119 , 120 ]. Atherosclerosis, autoimmune disease, diabetes mellitus, and inflammatory diseases are closely linked to the AGE receptor-ligand axis [ 121 , 122 , 123 , 124 ].…”

Section: Transporters and Receptors Of Uremic Toxins In The Endothmentioning

confidence: 99%

How do Uremic Toxins Affect the Endothelium?

Cunha

Santos

Barreto

et al. 2020

Toxins

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Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, such as transporters and receptors, can mediate the interaction between uremic toxins and endothelial cells. In these cells, uremic toxins induce oxidative stress and activation of signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways leads to overexpression of proinflammatory (e.g., monocyte chemoattractant protein-1, E-selectin) and prothrombotic (e.g., tissue factor) proteins. Uremic toxins also induce the formation of endothelial microparticles (EMPs), which can lead to the activation and dysfunction of other cells, and modulate the expression of microRNAs that have an important role in the regulation of cellular processes. The resulting endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases, such as atherosclerosis and thrombotic events. Therefore, uremic toxins as well as the pathways they modulated may be potential targets for therapies in order to improve treatment for patients with CKD.

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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

Cited by 24 publications

References 55 publications

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet‐Related Advanced Glycation End Products and Related 1,2‐Dicarbonyls

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet‐Related Advanced Glycation End Products and Related 1,2‐Dicarbonyls

Is skin autofluorescence (SAF) representative of dermal advanced glycation endproducts (AGEs) in dark skin? A pilot study

How do Uremic Toxins Affect the Endothelium?

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