Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2001-8-22
pubmed:abstractText
The toxic effect of thiram, a widely used dithiocarbamate fungicide, was investigated in cultured human skin fibroblasts. Cell survival assays demonstrated that thiram induced a dose-dependent decrease in the viable cell recovery. Thiram exposure resulted in a rapid depletion of intracellular reduced glutathione (GSH) content with a concomitant increase in oxidized glutathione (GSSG) concentration. Alteration of glutathione levels was accompanied by a dose-dependent decrease in the activity of glutathione reductase (GR), a key enzyme for the regeneration of GSH from GSSG. Thiram-exposed cells exhibited increased lipid peroxidation reflected by enhanced thiobarbituric acid reactive substances (TBARS) production, suggesting that GSH depletion and the lower GR activity gave rise to increased oxidative processes. To investigate the role of decreased GSH content in the toxicity of thiram, GSH levels were modulated prior to exposure. Pretreatment of fibroblasts with N-acetyl-L-cysteine (NAC), a GSH biosynthesis precursor, prevented both lipid peroxidation and cell death induced by thiram exposure. In contrast, thiram cytotoxicity was exacerbated by the previous depletion of cellular GSH by L-buthionine-(S,R)-sulfoximine (BSO). Taken together, these results strongly suggest that thiram induces GSH depletion, leading to oxidative stress and finally cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-62
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:11516525-Acetylcysteine, pubmed-meshheading:11516525-Adult, pubmed-meshheading:11516525-Buthionine Sulfoximine, pubmed-meshheading:11516525-Cell Death, pubmed-meshheading:11516525-Cell Division, pubmed-meshheading:11516525-Cell Survival, pubmed-meshheading:11516525-Cells, Cultured, pubmed-meshheading:11516525-Female, pubmed-meshheading:11516525-Fibroblasts, pubmed-meshheading:11516525-Fungicides, Industrial, pubmed-meshheading:11516525-Glutathione, pubmed-meshheading:11516525-Glutathione Disulfide, pubmed-meshheading:11516525-Glutathione Reductase, pubmed-meshheading:11516525-Humans, pubmed-meshheading:11516525-Lipid Peroxidation, pubmed-meshheading:11516525-Oxidation-Reduction, pubmed-meshheading:11516525-Thiobarbituric Acid Reactive Substances, pubmed-meshheading:11516525-Thiram
pubmed:year
2001
pubmed:articleTitle
Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death.
pubmed:affiliation
Laboratoire de Biochimie, UF Culture de Cellules, Centre Hospitalier Lyon-Sud, Chemin du Grand Revoyet, 69495 Pierre-Bénite Cedex, France. catherinecereser@hotmail.com
pubmed:publicationType
Journal Article