Advanced Glycation End Products in Clinical Nephrology

Abstract

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists).

Anthraquinones from the Seeds of Cassia tora with Inhibitory Activity on Protein Glycation and Aldose Reductase

“…28) In this study, emodin (6) and obtusifolin (8) exhibited much stronger inhibitory activity on AGEs-BSA formation (IC 50 values of 118 and 28.9 mM, respectively) than aminoguanidine (IC 50 value of 961 mM), a well known glycation inhibitor, while others were found to be inactive. The inhibitory effects of emodin (6) and obtusifolin (8) on AGEs-BSA formation in the assay were reconfirmed by a specific AGEs-ELISA (absorbance of 450 nm). As shown in Fig.…”

“…4) Direct evidence indicating the contribution of AGEs in the progression of diabetic complications in different lesions of the kidneys, the rat lens, and in atherosclerosis has been recently reported. 5,6) N e -Carboxymethyllysine (CML) is one of the best characterized compounds of AGEs and can be detected in tissue and serum proteins by specific antisera. 7) Aldose reductase (AR), the key enzyme in the polyol pathway, also has been demonstrated to play important roles in the pathogenesis of diabetic complications and cataract formation.…”

“…18) Previous phytochemical investigation on the seeds of C. tora have resulted in the isolation of several anthraquinone and naphthopyrone derivatives. 13,[16][17][18][19][20] In the present study, further fractionation of the EtOAc-soluble extract of the seeds of C. tora led to the purification of nine anthraquinones (1)(2)(3)(4)(5)(6)(7)(8)(9). The structures of 1-9 were determined by spectroscopic data interpretation and they were subjected to in vitro bioassays to evaluate their inhibitory activity against AGEs and RLAR.…”

The Antioxidative Effects of Astragalus Saponin I Protect Against Development of Early Diabetic Nephropathy

“…HbA1C is also one kind of amadori product, which appears in the early stage of DN, and its end product is AGEs. HbA1C is formed via nonenzymatic glycation which is specifically enhanced through the presence of oxidatants, and the ability to form glycoxidation products in peptide and protein structures finally modulates or induces biological reactivity (25). Therefore, the decreasing effect of AS I on HbA1C in vivo contributes to its antioxidative effect.…”

Diabetic Nephropathy: Current and Novel Therapeutic Approaches to Prevent Its Development and Progression

“…They often present as a yellow-brown pigmentation, may be fluorescent and a number are primarily cross-links between proteins (Brownlee 1992;Kalousova, Zima et al 2004). AGEs are formed as a result of non-enzymatic biochemical reactions initiated as part of the Maillard Reaction.…”