THIAMINE PYROPHOSPHATE AND PYRIDOXAMINE INHIBIT THE FORMATION OF ANTIGENIC ADVANCED GLYCATION END-PRODUCTS - COMPARISON WITH AMINOGUANIDINE

Nonenzymatic glycation of proteins by glucose leading to the formation of toxic and immunogenic advanced glycation end products (AGEs) may b e a major contributor to the pathological manifestations of diabetes m ellitus, aging, and, possibly, neurodegenerative diseases such as Alzh eimer's. We tested the in vitro inhibition of antigenic AGE formation on bovine serum albumin, ribonuclease A, and human hemoglobin by vario us vitamin B-1 and B-6 derivatives. Among the inhibitors, pyridoxamine and thiamine pyrophosphate potently inhibited AGE formation and were more effective than aminoguanidine, suggesting that these two compound s may have novel therapeutic potential in preventing vascular complica tions of diabetes. An unexpected finding was that aminoguanidine inhib ited the late kinetic stages of glycation much more weakly than the ea rly phase. (C) 1996 Academic Press, Inc.