Linked Life Data

12124304

Source:http://linkedlifedata.com/resource/pubmed/id/12124304

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-7-18
pubmed:abstractText
The kinetics of the reactions of glutathione (GSH) with 4-hydroperoxycyclophosphamide (4OOH-CP) and acrolein, a metabolite of 4OOH-CP, were investigated in a cell-free medium (pH approximately 7.5) and peripheral blood mononuclear cells. The ability of the thiol drugs, sodium 2-mercaptoethane sulfonate (mesna) and S-2-(3-aminopropylamino)ethanethiol (WR-1065), to affect the reactions of cellular GSH with the alkyalting agents was also studied. The amount of unreacted thiols in the various reactions was determined by derivatization with monobromobimane, followed by separation of fluorescent-labeled thioether adducts using high-pressure liquid chromatography. The second-order rate constants (k(2)) for reactions of GSH, mesna, and WR-1065 with 4OOH-CP in solution were 38 +/- 5, 25 +/- 5, and 880 +/- 50 M(-1) s(-1), respectively. The corresponding k(2) for reactions of GSH, mesna, and WR-1065 with acrolein were 490 +/- 100, 700 +/- 150, and >2000 M(-1) s(-1), respectively. The apparent rate constants for reactions of cellular GSH with acrolein and 4OOH-CP were smaller than those obtained in solution. Assuming that the k(2) is the same inside and outside cells, we estimate the first-order rate constant (k(1)) for transfer of 4OOH-CP and acrolein across the cell membrane as approximately 0.01 and approximately 0.04 s(-1), respectively. WR-1065 was more effective than mesna in blocking depletion of cellular GSH (because it passes into the cell more quickly and has higher reaction rates with the alkylators than the latter compound). When WR-1065 and mesna were used together, the protection against cellular depletion of GSH was additive. Our results are relevant to the administration of thiol drugs with high-dose alkylating agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
875-82
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Kinetic analysis of the reactions of 4-hydroperoxycyclophosphamide and acrolein with glutathione, mesna, and WR-1065.
pubmed:affiliation
Syracuse University, Department of Chemistry, Syracuse, New York, USA.
pubmed:publicationType
Journal Article, In Vitro