Urate attenuates oxidation of native low-density lipoprotein by hypochlorite and the subsequent lipoprotein-induced respiratory burst activities of polymorphonuclear leukocytes

Oxidation converts native low-density lipoprotein (LDL) into a signal molec ule promoting inflammatory processes during atherogenesis. The exact contri bution of different antioxidants in prevention of LDL oxidation is not know n. Uric acid efficiently scavenges oxidants including hypochlorite. We inve stigated the effect of different urate concentrations (25-500 mu mol/l) on the oxidation of isolated native LDL by sodium hypochlorite (1000 mu mol/l) . While relative electrophoretic mobility declined continuously with increa sing urate concentrations in the oxidation medium, lipid peroxidation as me asured by TBARS was blunted only at high molar urate/NaOCl ratios. By decre asing oxidative modifications, urate dose-dependently (beginning with a ura te/NaOCl ratio of 1:40) diminished stimulatory effects of oxidized LDL on t he respiratory burst of resting polymorphonuclear leukocytes (PMNL). Protec ting effects of urate against the proinflammatory action of oxidized LDL on activated cells were evident only at a molar urate/NaOCl ratio of 1:2 sugg esting different sensitivities of PMNL to LDL oxidation state in dependence on their activity state.