Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure.
Advanced glycation end products (AGEs) are senescent macroprotein derivatives that are formed at an accelerated rate in patients with chronic renal failure (CRF). AGE formation and accumulation in plasma and vascular tissues contribute to accelerated atherosclerosis in this devastating disorder. AST-120 is an oral adsorbent that attenuates the progression of CRF by removing uremic toxins. Recently, AST-120 has been reported to reduce the progression of atherosclerosis as well. However, whether AST-120 decreases serum levels of AGEs and subsequently exerts atheroprotective properties remains to be elucidated. Ten nondiabetic CRF patients were enrolled in this study. All patients were kept on regular therapeutic diet and medications throughout the study. Serum AGE levels before and after AST-120 treatments were measured using enzyme-linked immunosorbent assay. Effects of patient-derived serum on atherosclerosis-related gene expression in cultured human umbilical vein endothelial cells (HUVECs) were analyzed by semiquantitative RT-PCR. Administration of AST-120 (6 g/day) for 3 months significantly decreased serum levels of AGEs in nondiabetic CRF patients, whereas AGE levels remained unchanged in age- and renal function-matched CRF patients without AST-120 treatment (n = 6). Patient serum after AST-120 treatment significantly reduced mRNA levels of receptor for AGEs, monocyte chemoattractant protein-1, and vascular adhesion molecule-1 in HUVECs compared with serum before treatment. Moreover, in vitro, AST-120 was found to adsorb carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs. This study suggests that atheroprotective properties of AST-120 can be ascribed, at least in part, to its AGE-lowering ability via absorption of CML.
Ueda
Seiji
S
Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Yamagishi
Sho-ichi
S
Takeuchi
Masayoshi
M
Kohno
Keisuke
K
Shibata
Ryo
R
Matsumoto
Yuriko
Y
Kaneyuki
Utako
U
Fujimura
Toshiko
T
Hayashida
Ayako
A
Okuda
Seiya
S
D000284:Administration, Oral; D000327:Adsorption; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics; D002244:Carbon / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000494:pharmacology*
D017127:Glycation End Products, Advanced; D010087:Oxides; C048496:N(6)-carboxymethyllysine; D002244:Carbon; C040896:AST 120; D008239:Lysine