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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/4066

Title: Changes in expression of fibrotic markers and histopathological alterations in kidneys of mice chronically exposed to low and high Cd doses
Authors: THIJSSEN, Sandy
Issue Date: 2007
Citation: TOXICOLOGY, 238(2-3). p. 200-210
Abstract: The main target organ for cadmium (Cd) is the kidney, and more specifically the proximal tubular cells. Little is known about the effects of a long-term Cd exposure on the ultrastructure of the kidney and the involvement in tubulointerstitial fibrosis. Therefore, mice were exposed to Cd concentrations varying from 10 to 500 mg CdCl2/l in the drinking water during 4, 16 and 23 weeks. Ultrastructural changes were studied by means of light- and electron microscopical analyses. Furthermore, the expression of the extracellular matrix (ECM) proteins collagen I and fibronectin, and the myofibroblast/epithelial-to-mesenchymal transition (EMT) marker alfa-smooth muscle actin (alpha-SMA) were studied by means of immunohistochemistry. The histopathological changes caused by Cd varied considerably from one animal to another, and from one individual cell to another. An exposure to Cd concentrations up to 100 mg CdCl2/l elicited only minor changes that were restricted to increasing amounts of lysosomes and vacuolisation. When higher Cd concentrations were applied, the changes became more pronounced and featured mitochondrial damage, cellular swelling and loss of basal invaginations. An overproduction of the interstitial matrix component fibronectin and the expression of the myofibroblasts/EMT marker alpha-SMA in kidneys of mice exposed to 100 mg CdCl2/l clearly indicated that an exposure to relatively low Cd doses might lead ultimately to renal fibrosis. Increasing the Cd dose (up to 500 mg CdCl2/l) evoked an increased immunoreactivity for fibrotic markers. In conclusion we may state that concentrations up to 100 mg CdCl2/l evoked minor changes, although the expression of fibrotic markers was increased. Changes became more pronounced when exposing to higher Cd concentrations. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
Notes: Hasselt Univ, Ctr Environm Sci, Physiol Lab, Sch Life Sci,Transnatl Univ Limburg, B-3590 Diepenbeek, Belgium. Hasselt Univ, Inst Biomed Res, Sch Life Sci, Transnatl Univ Limburg, B-3590 Diepenbeek, Belgium. Hasselt Univ, Ctr Stat, B-3590 Diepenbeek, Belgium.VAN KERKHOVE, E, Hasselt Univ, Ctr Environm Sci, Physiol Lab, Sch Life Sci,Transnatl Univ Limburg, Agoralaan Bldg D, B-3590 Diepenbeek, Belgium.emmy.vankerkhove@uhasselt.be
URI: http://hdl.handle.net/1942/4066
DOI: 10.1016/j.tox.2007.06.087
ISI #: 000249542400014
ISSN: 0300-483X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2008
Appears in Collections: Research publications

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