Linked Life Data

8082231

Source:http://linkedlifedata.com/resource/pubmed/id/8082231

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-10-11
pubmed:abstractText
Neonatal rat heart myocytes were used to study the acute cardiotoxic effects of cyclophosphamide (CTX) metabolites. The myocytes were equi-sensitive to 4-hydroperoxycyclophosphamide (4HPC) and acrolein in vitro with 50% inhibitory concentrations (IC50) of 123 microM and 152 microM, respectively. The parent compound, CTX, was inactive and the myocytes were much less sensitive to the bis-chloroethylamine alkylator, mechlorethamine (IC50 = 1161 microM). Cellular glutathione (GSH) levels were initially reduced and then transiently elevated following exposure to 4HPC. With acrolein, GSH levels were reduced to unmeasurable levels at all time points. With the addition of 0.5 mM L-buthionine sulfoximine (BSO), myocyte GSH levels were reduced from control values of 120 nmol/mg protein to < 10 nmol/mg protein without causing direct cytotoxicity. However, pretreatment with BSO significantly enhanced the cardiotoxic effects of 4HPC. Finally, two exogenous sulfhydryl-containing compounds were shown to block the myotoxic effects of both 4HPC and acrolein. Mesna and N-acetylcysteine increased at concentrations of 0.01 microgram/ml and 0.1 microgram/ml roughly increased the IC50 of 4HPC by 2-3-fold. These results suggest that acrolein and 4HPC are equipotent cytotoxins and that a transient depletion in GSH accompanies this toxic effect in cardiac myocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-28
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Effect of sulfhydryl compounds and glutathione depletion on rat heart myocyte toxicity induced by 4-hydroperoxycyclophosphamide and acrolein in vitro.
pubmed:affiliation
Department of Pharmacology, University of Arizona, College of Medicine, Tucson 85724.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't