Pyridoxamine, an inhibitor of
advanced glycation and lipoxidation reactions: a novel therapy for
treatment of diabetic complications.
Metz TO, Alderson NL, Thorpe SR,
Baynes JW.
Department of Chemistry and Biochemistry,
Graduate Science Research Center,
University of South Carolina, Columbia, SC 29208
Arch Biochem Biophys. 2003 Nov
1;419(1):41-9.
Abstract
Pyridoxamine 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, Pyridoxamine
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. Pyridoxamine also inhibits the
development of retinopathy and neuropathy in the STZ-diabetic rat.
Several products of reaction of Pyridoxamine 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 Pyridoxamine as an
AGE/ALE inhibitor. Pyridoxamine 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
Pyridoxamine, and summarizes the results of animal model studies on the
use of Pyridoxamine for inhibiting AGE/ALE formation and development of
complications of diabetes and hyperlipidemia.
