Linked Life Data

11700947

Source:http://linkedlifedata.com/resource/pubmed/id/11700947

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-11-9
pubmed:abstractText
In the present study, we investigated the variation of endothelin (ET) levels in various organs (kidney, liver, spleen and heart) of rats after 7 and 15 days of Cyclosporine A (CsA) treatment. Moreover, we studied whether these modifications are related to major toxic effects, known to be a complication of CsA treatment (i. e. nephrotoxicity). The morphology of liver, spleen and heart in rats treated with CsA for 7 and 15 days was similar to that in control rats. The amounts of ET protein as determined by Western blot analysis were very low in all organs. However, we found lesions in kidneys of rats treated with CsA for 15 days but not in kidneys of rats treated for 7 days. Immunohistochemical analysis using an ET polyclonal antibody revealed that proximal tubules of animals treated for 15 days were strongly ET positive whereas distal tubules and glomerula showed only weak positivity as those in control rats. Western blot analysis revealed an increase in ET protein in treated rats. On the basis of these data, we conclude that CsA induced evident nephrotoxicity already after 15 days of treatment and that toxic effects of CsA were related to the amounts of ET found. An explanation for these findings is that ET, produced by epithelial cells, is filtered through the glomerular tuft and resorbed by tubular epithelial cells. Since variation in levels of ET was visible only in proximal tubules, we conclude that CsA treatment during a brief period produced side effects that can be considered as acute toxicity. Our finding may help to understand the mechanism of CsA toxicity and may provide important clues for pharmacological strategies to reduce CsA toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0065-1281
pubmed:author
pubmed:issnType
Print
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Induction of endothelin in rat kidney after cyclosporine A treatment.
pubmed:affiliation
Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't