Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-5-8
pubmed:abstractText
The kidney is one of the main targets of xenobiotic-induced toxicity, but early detection of renal damage is difficult. Recently, several novel biomarkers of nephrotoxicity have been identified by transcription profiling, including kidney injury molecule-1 (Kim-1), lipocalin-2, tissue inhibitor of metalloproteinases-1 (Timp-1), clusterin, osteopontin (OPN), and vimentin, and suggested as sensitive endpoints for acute kidney injury in vivo. However, it is not known if these cellular marker molecules may also be useful to predict chronic nephrotoxicity or to detect nephrotoxic effects in vitro. In this study, a panel of new biomarkers of renal toxicity was assessed via quantitative real-time PCR, immunohistochemistry, and immunoblotting in rats treated with the nephrotoxin ochratoxin A (OTA) for up to 90 days and in rat proximal tubule cells (NRK-52E) treated with OTA in vitro. Repeated administration of OTA to male F344/N rats for 14, 28, or 90 days resulted in a dose- and time-dependent increase in the expression of Kim-1, Timp-1, lipocalin-2, OPN, clusterin, and vimentin. Changes in gene expression were found to correlate with the progressive histopathological alterations and preceded effects on traditional clinical parameters indicative of impaired kidney function. Induction of Kim-1 messenger RNA expression was the earliest and most prominent response observed, supporting the use of this marker as sensitive indicator of chronic kidney injury. In contrast, no significant increase in the expression of putative marker genes and proteins were evident in NRK-52E cells after exposure to OTA for up to 48 h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, http://linkedlifedata.com/resource/pubmed/chemical/Formazans, http://linkedlifedata.com/resource/pubmed/chemical/Havcr1protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/MTT formazan, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Mycotoxins, http://linkedlifedata.com/resource/pubmed/chemical/Ochratoxins, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts, http://linkedlifedata.com/resource/pubmed/chemical/ochratoxin A
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-0929
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-81
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:18308701-Animals, pubmed-meshheading:18308701-Biological Markers, pubmed-meshheading:18308701-Carcinogens, pubmed-meshheading:18308701-Cell Adhesion Molecules, pubmed-meshheading:18308701-Cell Line, pubmed-meshheading:18308701-Cell Survival, pubmed-meshheading:18308701-Dose-Response Relationship, Drug, pubmed-meshheading:18308701-Formazans, pubmed-meshheading:18308701-Gene Expression, pubmed-meshheading:18308701-Immunoenzyme Techniques, pubmed-meshheading:18308701-Kidney Diseases, pubmed-meshheading:18308701-Kidney Tubules, Proximal, pubmed-meshheading:18308701-Male, pubmed-meshheading:18308701-Membrane Proteins, pubmed-meshheading:18308701-Mycotoxins, pubmed-meshheading:18308701-No-Observed-Adverse-Effect Level, pubmed-meshheading:18308701-Ochratoxins, pubmed-meshheading:18308701-RNA, Messenger, pubmed-meshheading:18308701-Rats, pubmed-meshheading:18308701-Rats, Inbred F344, pubmed-meshheading:18308701-Tetrazolium Salts
pubmed:year
2008
pubmed:articleTitle
Evaluation of putative biomarkers of nephrotoxicity after exposure to ochratoxin a in vivo and in vitro.
pubmed:affiliation
Department of Toxicology, University of Würzburg, Würzburg D-97078, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Evaluation Studies