Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications.
Pyridoxamine (PM), originally described as a post-Amadori inhibitor of formation of advanced glycation end-products (AGEs), also inhibits the formation of advanced lipoxidation end-products (ALEs) on protein during lipid peroxidation reactions. In addition to inhibition of AGE/ALE formation, PM has a strong lipid-lowering effect in streptozotocin (STZ)-induced diabetic and Zucker obese rats, and protects against the development of nephropathy in both animal models. PM also inhibits the development of retinopathy and neuropathy in the STZ-diabetic rat. Several products of reaction of PM with intermediates in lipid autoxidation have been identified in model reactions in vitro and in the urine of diabetic and obese rats, confirming the action of PM as an AGE/ALE inhibitor. PM appears to act by a mechanism analogous to that of AGE-breakers, by reaction with dicarbonyl intermediates in AGE/ALE formation. This review summarizes current knowledge on the mechanism of formation of AGE/ALEs, proposes a mechanism of action of PM, and summarizes the results of animal model studies on the use of PM for inhibiting AGE/ALE formation and development of complications of diabetes and hyperlipidemia.
Metz
Thomas O
TO
Department of Chemistry and Biochemistry, Graduate Science Research Center, University of South Carolina, Columbia, SC 29208, USA.
Alderson
Nathan L
NL
Thorpe
Suzanne R
SR
Baynes
John W
JW
D000818:Animals; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D015394:Molecular Structure; D011733:Pyridoxamine / Q000737:chemistry / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D011733:Pyridoxamine