title: Inhibition of iron-catalyzed oxidations by attainable uric acid and ascorbic acid levels: therapeutic implications for Alzheimer's disease and late cognitive impairment.
abstract: BACKGROUND
  Alzheimer's disease (AD) has become one of the major health problems of the developed world. Previous studies have shown that oxidant-induced changes occur in cerebral tissue in AD and in late-onset amnestic mild cognitive impairment. The oxidative damage begins early and involves free radical-mediated effects that cause lipid peroxidations and oxidative protein and nucleic acid damages which begin before the cardinal neuropathologic manifestations. Impaired cerebral iron homeostasis and iron accumulation are postulated to be primary and seminal in the pathogenesis.
  
  
  OBJECTIVE
  To demonstrate that the Fenton reaction involving hydrogen peroxide and iron at very low concentrations as has been found in human plasma and cerebrospinal fluid may produce promptly oxidations which may be inhibited by preventive use of uric acid and ascorbic acid as hydrophilic antioxidants.
  
  
  METHODS
  A photometric study in vitro at physiologic pH using concentrations of uric acid and ascorbic acid readily attainable in human extracellular fluids.
  
  
  RESULTS
  Uric acid levels of 0.5 and 6.0 mg/dl (below the saturation level for urate precipitation) and ascorbic acid at a level readily attainable in blood plasma inhibited significantly and completely, respectively, oxidations caused by reactions of 20 microM concentrations of hydrogen peroxide with free bivalent iron at 9.8 muM and at a low hemoglobin level of 12 mg/dl of saline.
  
  
  CONCLUSIONS
  Results suggest that supplemental use orally of ascorbic acid combined with use of metabolic precursor to uric acid, like inosine or hypoxanthine, has the potential for preventing or attenuating the progression of AD and amnestic mild cognitive impairment.
authors: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
authors: William H
authors: WH
authors: Waugh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006454:Hemoglobins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000009:adverse effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010783:Photometry; D014527:Uric Acid / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D006454:Hemoglobins; D014527:Uric Acid; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid