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 molecule promoting inflammatory processes during atherogenesis. The exact contribution of different antioxidants in prevention of LDL oxidation is not known. Uric acid efficiently scavenges oxidants including hypochlorite. We investigated the effect of different urate concentrations (25-500 micromol/l) on the oxidation of isolated native LDL by sodium hypochlorite (1000 micromol/l). While relative electrophoretic mobility declined continuously with increasing urate concentrations in the oxidation medium, lipid peroxidation as measured by TBARS was blunted only at high molar urate/NaOCl ratios. By decreasing oxidative modifications, urate dose-dependently (beginning with a urate/NaOCl ratio of 1:40) diminished stimulatory effects of oxidized LDL on the respiratory burst of resting polymorphonuclear leukocytes (PMNL). Protecting 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 suggesting different sensitivities of PMNL to LDL oxidation state in dependence on their activity state.
Kopprasch
S
S
Department of Internal Medicine III, Pathological Biochemistry, Carl Gustav Carus Medical School, Technical University of Dresden, Germany. Skoppras@rcs1.urz.tu-dresden.de
Richter
K
K
Leonhardt
W
W
Pietzsch
J
J
Grässler
J
J
D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D016166:Free Radical Scavengers; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008163:Luminescent Measurements; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D016897:Respiratory Burst / Q000502:physiology; D012973:Sodium Hypochlorite / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014527:Uric Acid / Q000494:pharmacology*
D000975:Antioxidants; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014527:Uric Acid; D012973:Sodium Hypochlorite