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 be a major contributor to the pathological manifestations of diabetes mellitus, aging, and, possibly, neurodegenerative diseases such as Alzheimer's. We tested the in vitro inhibition of antigenic AGE formation on bovine serum albumin, ribonuclease A, and human hemoglobin by various vitamin B1 and B6 derivatives. Among the inhibitors, pyridoxamine and thiamine pyrophosphate potently inhibited AGE formation and were more effective than aminoguanidine, suggesting that these two compounds may have novel therapeutic potential in preventing vascular complications of diabetes. An unexpected finding was that aminoguanidine inhibited the late kinetic stages of glycation much more weakly than the early phase.
Booth
A A
AA
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160-7421, USA.
Khalifah
R G
RG
Hudson
B G
BG
D000818:Animals; D000941:Antigens / Q000096:biosynthesis; D002417:Cattle; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000096:biosynthesis* / Q000276:immunology*; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008706:Methemoglobin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011733:Pyridoxamine / Q000494:pharmacology*; D011817:Rabbits; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000494:pharmacology*
D000941:Antigens; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D012710:Serum Albumin, Bovine; D011733:Pyridoxamine; D008706:Methemoglobin; D012259:Ribonuclease, Pancreatic; D013835:Thiamine Pyrophosphate; C004479:pimagedine