Linked Life Data

3401242

Source:http://linkedlifedata.com/resource/pubmed/id/3401242

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1988-9-2
pubmed:abstractText
Freshly isolated rat hepatocytes were used to study the mechanism(s) of toxicity of the antimicrobial drug nitrofurantoin. This 5-nitrofuran derivative stimulated hepatocyte oxygen uptake in the presence of the mitochondrial respiration inhibitors KCN or antimycin A. This could indicate the formation of O2- and H2O2, following intracellular nitrofurantoin reduction. Addition of nitrofurantoin to suspensions of isolated rat hepatocytes produced a dose- and time-dependent decrease of cell viability. H2O2 probably plays a significant role in the cytotoxic effects of nitrofurantoin as the catalase inhibitors azide or aminotriazole markedly enhanced cytotoxicity. The loss of cell viability was preceded by glutathione (GSH) depletion and a concomitant and nearly stoichiometric formation of oxidised glutathione (GSSG) that did not occur in hepatocytes lacking glutathione peroxidase activity isolated from rats fed a low-selenium diet. This indicates that H2O2 and the seleno-enzyme glutathione peroxidase are responsible for GSH oxidation. Furthermore, addition of nitrofurantoin to isolated rat hepatocytes produced a reversible inactivation of hepatocyte glutathione reductase activity and explains the maintenance of high GSSG levels. The compromised hepatocytes were also highly susceptible to H2O2. The hepatocyte toxicity of nitrofurantoin may, therefore, be attributed to oxidative stress caused by redox-cycling mediated oxygen activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3109-17
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Nitrofurantoin-mediated oxidative stress cytotoxicity in isolated rat hepatocytes.
pubmed:affiliation
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't