Increased Production of Urea Hydrogen Peroxide from Maillard Reaction and a UHP-Fenton Pathway Related to Glycoxidation Damage in Chronic Renal Failure

Abstract

Urea hydrogen peroxide (UHP) is a stable form of H(2)O(2) and cytotoxic agent. This study describes examination of UHP formation from collagen glycation and relevant glycoxidative damage in chronic renal failure (CRF). Renal fibers were incubated with 50 mM ribose in either serum ultrafiltrate or phosphate-buffered saline in the presence of various concentrations of urea. UHP was determined by a modified ferrous oxidation in xylenol orange (FOX) assay. The presence of urea resulted in an increase in the generation of UHP in a dose-dependent manner of urea in these incubation systems. Pentosidine levels analyzed by HPLC also increased in a dose-dependent manner of urea. Blocking experiments showed that pentosidine and carboxymethyllysine formation was significantly enhanced by hydroxyl radical generated from UHP via Fenton reaction. The renal and cardiac levels of UHP, pentosidine, and carboxymethyllysine in patients with CRF, including seven predialysis and eight hemodialysis subjects, were significantly higher than that in controls (n = 16). The renal and cardiac levels of UHP closely correlated with the levels of renal and cardiac pentosidine and carboxymethyllysine and inversely correlated with left ventricle ejection fraction in CRF patients. This study provides evidence, for the first time, that UHP can be produced from Maillard reaction. Increased UHP in chronic renal failure enhances the formation of pentosidine and carboxymethyllysine via Fenton reaction (UHP-Fenton pathway).