Linked Life Data

7548755

Source:http://linkedlifedata.com/resource/pubmed/id/7548755

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-11-14
pubmed:abstractText
We have characterized a chemically reactive propranolol (PL) metabolite which binds to proteins in rat liver microsomes. During incubation with rat liver microsomes (1 mg of protein) fortified with an NADPH-generating system, 4-hydroxypropranolol (4-OH-PL) quickly disappeared from the reaction medium, but none of the possible metabolite peaks was detected under the high-performance liquid chromatographic conditions used. The consumption of 4-OH-PL depended on microsomes and NADPH. The reaction was not affected by inhibitors of cytochrome P450 or FAD monooxygenase, but was markedly diminished in the presence of cytosol and ascorbic acid. The effect of cytosol was inhibited by potassium cyanide but not by sodium benzoate or dimethyl sulfoxide, and was also not affected by heating at 60 degrees C for 30 min, suggesting that superoxide (SO) ion was involved in the reaction and that it was blocked by superoxide dismutase (SOD) present in the cytosol. Cu,Zn-SOD, purified from cytosol, effectively mimicked the suppressive effect of cytosol. Incubation of 4-OH-PL in an SO-generating system of xanthine and xanthine oxidase generated 1,4-naphthoquinone (1,4-NQ), which was identified by TLC, HPLC, and GC/MS. 1,4-NQ was also formed in microsomal incubates containing NADPH and small amounts of microsomes (below 0.1 mg of protein). These results indicate that 4-OH-PL is converted by SO, or some reactive oxygen species derived from it, to 1,4-NQ which binds to proteins and is one of the reactive metabolites of PL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
721-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:articleTitle
Characterization of a chemically reactive propranolol metabolite that binds to microsomal proteins of rat liver.
pubmed:affiliation
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
pubmed:publicationType
Journal Article