Oxidative stress-inducing carbonyl compounds from common foods: novel mediators of cellular dysfunction

Mol Med. 2002 Jul;8(7):337-46.


Background: The general increase in reactive oxygen species generated from glucose-derived advanced glycation endproducts (AGEs) is among the key mechanisms implicated in tissue injury due to diabetes. AGE-rich foods could exacerbate diabetic injury, at least by raising the endogenous AGE.

Materials and methods: Herein, we tested whether, prior to ingestion, diet-derived AGEs contain species with cell activating (TNFalpha), chemical (cross-linking) or cell oxidative properties, similar to native AGEs. Glutathione (GSH) and GSH peroxidase (GPx) were assessed after exposure of human umbilical vein endothelial cell (HUVECs) to affinity-purified food-AGE extracts, each exposed to 250 degrees C, for 10 min, along with synthetic AGEs.

Results: Animal product-derived AGE, like synthetic methylglyoxal-bovine serum albumin (MG-BSA), AGE-BSA, and AGE-low density lipoprotein (AGE-LDL), induced a dose- and time-dependent depletion of GSH (()60-75%, p, 0.01) and an increase in GPx activity (()500-600%, p < 0.01), consistent with marked TNFalpha and cross-link formation (p < 0.05); this contrasted with the low bioreactivity of starch/vegetable AGE-extracts, which was similar to that of control BSA and CML- BSA and BSA (p:NS). Anti-AGE-R1,2,3 and -RAGE IgG each inhibited cell-associated (125) I-dAGE by approximately 30-55%; GSH/GPx were effectively blocked by N-acetyl-cysteine (NAC, 800 uM, p < 0.01) and aminoguanidine-HCl (AG, 100 uM, p < 0.01).

Conclusion: Thus, food-derived AGE, prior to absorption, contain potent carbonyl species, that can induce oxidative stress and promote inflammatory signals.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Cattle
  • Cells, Cultured
  • Cross-Linking Reagents / chemistry
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Food / adverse effects*
  • Glutathione / analysis
  • Glutathione Peroxidase / analysis
  • Glycation End Products, Advanced / chemical synthesis
  • Glycation End Products, Advanced / pharmacology*
  • Guanidines / pharmacology
  • Humans
  • Lipoproteins, LDL / analysis
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Umbilical Veins / cytology


  • Cross-Linking Reagents
  • Glycation End Products, Advanced
  • Guanidines
  • Lipoproteins, LDL
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Glutathione Peroxidase
  • Glutathione
  • pimagedine
  • Acetylcysteine