Differences in kinetics and dynamics of endogenous versus exogenous advanced glycation end products (AGEs) and their precursors. (June 2022)

• Record Type: Journal Article
• Authors: van Dongen, Katja C.W.; Kappetein, Leonie; Miro Estruch, Ignacio; Belzer, Clara; Beekmann, Karsten; Rietjens, Ivonne M.C.M.
• Is Part Of: Food and chemical toxicology. Volume 164(2022)
• Publication Date: 2022-06
• Subjects: ADME -- Dicarbonyls -- Gut microbiota -- RAGE -- Cross-linking -- Dicarbonyl stress; ADME absorption, distribution, metabolism, excretion -- AGE advanced glycation end product -- AGE-R1 oligosaccaharyltransferase-48 -- AGE-R2 80K-H phosphoprotein -- ALE advanced lipoxidation end product -- BSA bovine serum albumin -- CEL Nɛ-(carboxyethyl)lysine -- CML Nɛ-(carboxymethyl)lysine -- FL fructoselysine -- HbA1C glycated hemoglobin -- HMF hydroxymethylfurfural -- HMM high molecular mass -- LC-MS/MS liquid chromatography tandem mass spectrometry -- LDL low density lipoproteins -- LMM low molecular mass -- MAPK mitogen-activated protein kinases -- MG-H1 Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine -- NF-κB nuclear factor-kappa B -- NOD non-obese diabetic -- Nrf2 nuclear factor erythroid 2-related factor 2 -- PUFA polyunsaturated fatty acid -- RAGE receptor for AGE -- ROS reactive oxygen species -- SCFA short chain fatty acid -- sRAGE soluble RAGE; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.112987
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Advanced glycation end products (AGEs) and their precursors, referred to as glycation products, are a heterogenous group of compounds being associated with adverse health effects. They are formed endogenously and in exogenous sources including food. This review investigates the roles of endogenously versus exogenously formed glycation products in the potential induction of adverse health effects, focusing on differences in toxicokinetics and toxicodynamics, which appeared to differ depending on the molecular mass of the glycation product. Based on the available data, exogenous low molecular mass (LMM) glycation products seem to be bioavailable and to contribute to dicarbonyl stress and protein cross-linking resulting in formation of endogenous AGEs. Bioavailability of exogenous high molecular mass (HMM) glycation products appears limited, while these bind to the AGE receptor (RAGE), initiating adverse health effects. Together, this suggests that RAGE-binding in relevant tissues will more likely result from endogenously formed glycation products. Effects on gut microbiota induced by glycation products is proposed as a third mode of action. Overall, studies which better discriminate between LMM and HMM glycation products and between endogenous and exogenous formation are needed to further elucidate the contributions of these different types and sources of glycation products to the ultimate biological effects. Highlights: The molecular mass of glycation products influences their kinetics and dynamics. Systemic exposure to HMM glycation products depends on their endogenous formation from precursors. Future research on AGEs should distinguish between levels originating from endogenous versus exogenous formation.