Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Ferrous ion autoxidation and its chelation in iron-loaded human liver HepG2 cells.

Authors
Huang-X; Dai-J; Fournier-J; Ali-AM; Zhang-Q; Frenkel-K
Source
Free Radic Biol Med 2002 Jan; 32(1):84-92
NIOSHTIC No.
20029529
Abstract
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.
Keywords
Chelates; Liver; Iron-compounds; Iron-oxides; Ferrous-metals
Contact
Nelson Institute of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016-6451
CODEN
FRBMEH
Publication Date
20020101
Document Type
Journal Article
Email Address
xihuang@env.med.nyu.edu
Funding Amount
638746
Funding Type
Grant
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003561
Issue of Publication
1
ISSN
0891-5849
Source Name
Free Radical Biology and Medicine
State
NY
Performing Organization
New York University Medical Center, New York, New York
TOP