3-4-dideoxyglucosone-3-ene and Inflammation

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-

Topics: Apoptosis; Deoxyglucose; Galactose; Glycation End Products, Advanced; Humans; In Vitro Techniques; Inflammation; Keratinocytes; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Pyrones; Reactive Oxygen Species

Hyperglycaemia and glucose degradation products (GDPs) are closely associated with oxidative stress and inflammation in diabetic patients, a condition that leads to endothelial dysfunction and cardiovascular problems. We evaluated the effect of citrate and gluconate on glucose- and GDP-induced endothelial inflammation by measuring changes in viability, inflammation and function in primary human umbilical vein endothelial cells (HUVECs). The extent of apoptosis/necrosis was measured by flow cytometry and visualised with confocal microscopy by staining with annexin V or propidium iodide, respectively. Protein kinase C-βII (PKC-βII) activation was evaluated with Western blotting. Incubation with glucose (30 mM) and GDP (50 µM) significantly increased PKC-βII expression, endothelial cell death and inflammation. The addition of citrate decreased hyperglycaemia-induced apoptosis (p = 0.021), necrosis (p = 0.04) and reduced PKC-βII expression (p = 0.021) down to background levels. Citrate improved endothelial function by reducing the inflammatory markers (p = 0.01) and by decreasing neutrophil diapedesis (p = 0.012). These results suggest that citrate may have therapeutic potential by reducing hyperglycaemia-induced endothelial inflammation and abolishing endothelial dysfunction.

Topics: Anti-Inflammatory Agents; Apoptosis; Blotting, Western; Cell Survival; Cells, Cultured; Citric Acid; Coculture Techniques; Enzyme Activation; Flow Cytometry; Gluconates; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Inflammation; Intercellular Adhesion Molecule-1; Microscopy, Confocal; Necrosis; Neutrophils; Protein Kinase C; Protein Kinase C beta; Pyrones; Transendothelial and Transepithelial Migration