Linked Life Data

12018998

Source:http://linkedlifedata.com/resource/pubmed/id/12018998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-5-20
pubmed:abstractText
The use of spin-trapping agents for a direct ESR detection of *OH in biological systems is limited by the low stability of the hydroxyl radical-derived nitroxides. Among the various probes used for trapping of *OH, DMSO has proven to be highly efficient. The reaction between *OH and DMSO yields methyl radical (CH(3)*), which can react with N-tert-butyl-alpha-phenylnitrone (PBN) and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) to form stable, ESR-detectable nitroxides. The latter approach has been successfully used in in vivo experiments for analysis of *OH; in these experiments, POBN/*CH(3) and PBN/*CH(3) were detected in the bile duct and the urine of the treated animals. However, the sites of generation of *OH produced in vivo are unknown. Currently, no ESR data is available for the formation of *OH in liver of animals subjected to oxidative stress. Since nitroxides containing aromatic rings are likely to be substrates of cytochrome P450, experiments were carried out for assessing the ability of the cytochrome P450 monooxygenase system to metabolize PBN/*CH(3) and POBN/*CH(3), respectively. In the presence of NADPH, rat liver microsomes catalyzed the reduction of POBN/*CH(3) to the corresponding hydroxylamine (POBN/CH(3)), while PBN/*CH(3) was metabolized without accumulation of its hydroxylamine form (PBN/CH(3)). The metabolism of PBN/.CH(3) was inhibited by 4-methylpyrazole and ketoconasole, suggesting that cytochrome P450-catalysis was required for the consumption of this nitroxide. Under anaerobic conditions, both the nitroxide and hydroxylamine forms of PBN/CH(3) were metabolized, implying that these adducts may undergo reductive cytochrome P450-catalyzed biotransformation. On the basis of the susceptibility of PBN/*CH(3) to undergo irreversible metabolic transformation, it is discussed that POBN may prove to be a more efficient spin-trapping agent for the in vivo detection of *OH.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
749-53
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Comparative metabolism of N-tert-butyl-N-[1-(1-oxy-pyridin-4-yl)-ethyl]- and N-tert-butyl-N-(1-phenyl-ethyl)-nitroxide by the cytochrome P450 monooxygenase system.
pubmed:affiliation
Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.