Linked Life Data

12957295

Source:http://linkedlifedata.com/resource/pubmed/id/12957295

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-9-5
pubmed:abstractText
Iron plays a critical role in catalyzing the formation of potent oxidants. Increases in iron content enhance oxidative stress, whereas removal of iron deceases such stress. An association between iron and alcoholic liver injury has been proposed. The ability of iron to modulate the biochemical and toxicologic actions of cytochrome P450 2E1 (CYP2E1) has been evaluated by using isolated microsomes and intact liver cells. The ability of different iron complexes to stimulate microsomal lipid peroxidation and hydroxyl radical production during reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)- and reduced form of nicotinamide adenine dinucleotide (NADH)-dependent electron transfer has been characterized. Certain iron complexes have been shown to be effective in promoting lipid peroxidation; others are better catalysts of hydroxyl radical production as a complex pattern has been found. Reactive oxygen production, lipid peroxidation, and interaction with iron chelates have been shown to be enhanced with microsomes isolated from ethanol-treated rats with elevated levels of CYP2E1. This increase was prevented by anti-CYP2E1 immunoglobulin (Ig)G or chemical inhibitors of CYP2E1. Thus, in the presence of iron complexes, microsomes enriched in CYP2E1 are especially reactive in generation of reactive oxygen species. To assess the toxicologic significance of this iron-CYP2E1 interaction, iron (ferric-nitrilotriacetate) was added to HepG2 cells, which were engineered to express the human CYP2E1. Ferric-nitrilotriacetate produced a greater toxicity in the CYP2E1-expressing HepG2 cells than that in control HepG2 cells. This enhanced, synergistic toxicity was blocked by antioxidants and inhibitors of CYP2E1. Mitochondrial membrane potential and ATP levels were decreased, and damage to the mitochondria played a critical role in the CYP2E1-plus-iron-dependent toxicity. These results support the suggestion that low concentrations of iron and polyunsaturated fatty acids can act as priming or sensitizing factors for CYP2E1-induced injury in HepG2 cells and hepatocytes. Such interactions may play a role in alcohol-induced liver injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0741-8329
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
115-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Iron and CYP2E1-dependent oxidative stress and toxicity.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, New York, NY 10029, USA. arthur.cederbaum@mssm.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review