Linked Life Data

9928683

Source:http://linkedlifedata.com/resource/pubmed/id/9928683

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-5-3
pubmed:abstractText
Chronic human exposure to Cd results in kidney injury. It has been proposed that nephrotoxicity produced by chronic Cd exposure is via the Cd-metallothionein complex (CdMT) and not by inorganic forms of Cd. If this hypothesis is correct, then MT-null mice, which cannot form CdMT, should not develop nephrotoxicity. Control and MT-null mice were injected s.c. with a wide range of CdCl2 doses, six times/week for up to 10 weeks, and their renal Cd burden, renal MT concentration, and nephrotoxicity were quantified. In control mice, renal Cd burden increased in a dose- and time-dependent manner, reaching as high as 140 microg Cd/g kidney, along with 150-fold increases in renal MT concentrations, reaching 800 microg MT/g kidney. In MT-null mice, renal Cd concentration (10 microg/g) was much lower, and renal MT was nonexistent. The maximum tolerated dose of Cd in MT-null mice was approximately one-eighth that of controls. MT-null mice were more susceptible than controls to Cd-induced renal injury, as evidenced by increased urinary excretion of protein, glucose, gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, as well as by increased blood urea nitrogen levels. Kidneys of Cd-treated mice were enlarged and histopathology showed various types of lesions, including proximal tubular degeneration, apoptosis, atrophy, interstitial inflammation, and glomerular swelling. These lesions were more severe in MT-null than in control mice, mirroring the biochemical analyses. These data indicate that Cd-induced renal injury is not necessarily mediated through the CdMT complex and that MT is an important intracellular protein in protecting against chronic Cd nephrotoxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
197-203
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Susceptibility of MT-null mice to chronic CdCl2-induced nephrotoxicity indicates that renal injury is not mediated by the CdMT complex.
pubmed:affiliation
Center for Environmental and Occupational Health, Department of Pharmacology, Toxicoloy & Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't