Ferrous Ion Autoxidation and Its Chelation in Iron-Loaded Human Liver HepG2 Cells

Details

• Personal Author:
  Ali AM ; Dai J ; Fournier J ; Frenkel K ; Huang X ; Zhang Q
• Description:
  Ferrous ion (Fe(2+)) is long thought to be the most likely active species, producing oxidants through interaction of Fe(2+) with oxygen (O(2)). Because current iron overload therapy uses only Fe(3+) chelators, such as desferrioxamine (DFO), we have tested a hypothesis that addition of a Fe(2+) chelator, 2,2'-dipyridyl (DP), may be more efficient and effective in preventing iron-induced oxidative damage in human liver HepG2 cells than DFO alone. Using ferrozine as an assay for iron measurement, levels of cellular iron in HepG2 cells treated with iron compounds correlated well with the extent of lipid peroxidation (r = 0.99 after log transformation). DP or DFO alone decreased levels of iron and lipid peroxidation in cells treated with iron. DFO + DP together had the most significant effect in preventing cells from lipid peroxidation but not as effective in decreasing overall iron levels in the cells. Using ESR spin trapping technique, we further tested factors that can affect oxidant-producing activity of Fe(2+) with dissolved O(2) in a cell-free system. Oxidant formation enhanced with increasing Fe(2+) concentrations and reached a maximum at 5 mM of Fe(2+). When the concentration of Fe(2+) was increased to 50 mM, the oxidant-producing activity of Fe(2+) sharply decreased to zero. The initial ratio of Fe(3+):Fe(2+) did not affect the oxidant producing activity of Fe(2+). However, an acidic pH (< 3.5) significantly slowed down the rate of the reaction. Our results suggest that reaction of Fe(2+) with O(2) is an important one for oxidant formation in biological system, and therefore, drugs capable of inhibiting redox activity of Fe(2+) should be considered in combination with a Fe(3+) chelator for iron overload chelation therapy. [Description provided by NIOSH]
• Subjects:
  Chelating Agents Ferrous Compounds Occupational Health Safety
• Keywords:
  Chelates Ferrous-metals Iron-compounds Iron-oxides Liver
• ISSN:
  0891-5849
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  84-92
• Volume:
  32
• Issue:
  1
• NIOSHTIC Number:
  nn:20029529
• Citation:
  Free Radic Biol Med 2002 Jan; 32(1):84-92
• Contact Point Address:
  Nelson Institute of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016-6451
• Email:
  xihuang@env.med.nyu.edu
• Federal Fiscal Year:
  2002
• Performing Organization:
  New York University Medical Center, New York, New York
• Peer Reviewed:
  True
• Start Date:
  19990930
• Source Full Name:
  Free Radical Biology and Medicine
• End Date:
  20030929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b898b273e996cb582647d2ddbf82052883c08194e901aa749ece396e6670781db0c40d2d465a2af178d4b68d9e9d828969313ed8a6e31b230cb9d6797cbdf3d7
• Download URL:
  https://stacks.cdc.gov/view/cdc/190485/cdc_190485_DS1.pdf
• File Type:
  [PDF - 131.89 KB ]