Alcoholic Liver Disease Is Associated with Elevated Plasma Levels of Novel Advanced Glycation End-Products: A Preliminary Study

Abstract

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 μg/mL and 123.5 ± 44.9 μg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10.

Novel In Vitro Assay of the Effects of Kampo Medicines against Intra/Extracellular Advanced Glycation End-Products in Oral, Esophageal, and Gastric Epithelial Cells

“…They investigated various generation conditions, such as the concentration of lysine, reaction time, and temperature, and found that CEL was generated at much higher proportions than CML under the same condition (CEL >> CML). Litwinowicz et al determined the structure of novel melibiose-derived AGEs (MAGE) and classified them as AGE-10 [ 63 ].…”

Analysis of Crude, Diverse, and Multiple Advanced Glycation End-Product Patterns May Be Important and Beneficial

“…These AGEs can induce cytotoxicity, thereby including inflammation, because RAGE and TRL4 are expressed on the surfaces of various cells [ 1 , 11 , 26 ]. Furthermore, researchers have attempted to show that AGEs in the fluid correlate with the onset/progression of specific diseases, proving that AGEs could be biomarkers for these diseases [ 11 , 18 , 19 , 23 , 24 , 69 , 70 , 71 ]. The most beneficial and authentic biomarkers are (i) generated in specific organs and (ii) detected upon disease onset/progression, or organ dysfunction [ 72 , 73 , 74 , 75 ].…”

“…Notably, Kato et al simultaneously analyzed four AGEs [CML, CEL, N δ -(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (5-hydroxy-5-methylimidazolone) (MG-H1), and N ω -carboxymethyl-arginine (CMA)] in the serum of nephropathy patients using LC-ESI-MS and showed that MG-H1 dramatically increased relative to the other three AGEs [ 70 ]. Lirwinowicz et al determined the structure of a synthetic, melibiose-derived AGE (MAGE) and showed that MAGE in plasma correlated with NASH in a clinical study [ 71 ]. Although the structure of TAGE remains unclear, serum TAGE levels are associated with DM, CVD, NASH, infertility, cancer, and Alzheimer’s disease [ 5 ] and may be rare biomarkers with utility in determining the risk of various LSRDs.…”

“…Wang et al reported that CML-modified proteins in a rat cardiomyocyte cell line (H9c2) treated with methylglyoxal increased, as shown by Western blotting [ 97 ]. Litwinowicz et al classified the MAGE that they synthesized as AGE-10 [ 71 ]. The categories of MGO-AGEs and GA-AGEs may change in the future ( Figure 4 ).…”