Quantitative assessment of organ distribution of dietary protein‐bound 13C‐labeled Nɛ‐carboxymethyllysine after a chronic oral exposure in mice

cope Nɛ-Carboxymethyl-lysine (CML) is a prominent advanced glycation end-product which is not only found in vivo but also in food. It is known that a percentage of the dietary CML (dCML) is absorbed into the circulation and only partly excreted in the urine. Several studies have tried to measure how much dCML remains in tissues. However obstacles to interpreting the data have been found. Methods and results A new protocol which discriminates dCML from native CML (nCML) has been developed. Three CML isotopes with different mass-to-charge ratios were used: nCML Ne-carboxymethyl-L-lysine, dCML Ne-[13C]carboxy[13C]methyl-L-lysine and internal standard Ne-carboxymethyl-L-[4,4,5,5-2H4]lysine. Wild-type (n = 7) and RAGE−/− (n = 8) mice were fed for 30 days with either a control, or a BSA-bound dCML-enriched diet. Organs were analyzed for nCML and dCML using liquid chromatography–tandem mass spectrometry. Mice exposed to dCML showed an accumulation in all tissues tested except fat. The rate of deposition was high (81–320 μgdCML/g dry matter) in kidneys, intestine, and lungs and low (<5 μg/g) in heart, muscle, and liver. This accumulation was not RAGE dependent. Conclusion The kidney is not the only organ affected by the accumulation of dCML. Its high accumulation in other tissues and organs may also, however, have important physiological consequences.