Changes in expression of fibrotic markers and histopathological alterations in kidneys of mice chronically exposed to low and high Cd doses.
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 CdCl(2)/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 100mg CdCl(2)/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 100mg CdCl(2)/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 CdCl(2)/l) evoked an increased immunoreactivity for fibrotic markers. In conclusion we may state that concentrations up to 100mg CdCl(2)/l evoked minor changes, although the expression of fibrotic markers was increased. Changes became more pronounced when exposing to higher Cd concentrations.
Thijssen
Sandy
S
Centre for Environmental Sciences, transnationale Universiteit Limburg, School of Life Sciences, Hasselt University, Agoralaan Building D, 3590 Diepenbeek, Belgium. sandy_thijssen@hotmail.com
Lambrichts
Ivo
I
Maringwa
John
J
Van Kerkhove
Emmy
E
D000199:Actins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007120:Immunochemistry; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
C558396:Acta2 protein, mouse; D000199:Actins; D015415:Biomarkers; D024042:Collagen Type I; D005353:Fibronectins; D019256:Cadmium Chloride