Document Detail


Mechanisms of cadmium-induced proximal tubule injury: new insights with implications for biomonitoring and therapeutic interventions.
MedLine Citation:
PMID:  22669569     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cadmium is an important industrial agent and environmental pollutant that is a major cause of kidney disease. With chronic exposure, cadmium accumulates in the epithelial cells of the proximal tubule, resulting in a generalized reabsorptive dysfunction characterized by polyuria and low-molecular-weight proteinuria. The traditional view has been that as cadmium accumulates in proximal tubule cells, it produces a variety of relatively nonspecific toxic effects that result in the death of renal epithelial cells through necrotic or apoptotic mechanisms. However, a growing volume of evidence suggests that rather than merely being a consequence of cell death, the early stages of cadmium-induced proximal tubule injury may involve much more specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic responses that occur well before the onset of necrosis or apoptosis. In this commentary, we summarize these recent findings, and we offer our own perspectives as to how they relate to the toxic actions of cadmium in the kidney. In addition, we highlight recent findings, suggesting that it may be possible to detect the early stages of cadmium toxicity through the use of improved biomarkers. Finally, some of the therapeutic implications of these findings will be considered. Because cadmium is, in many respects, a model cumulative nephrotoxicant, these insights may have broader implications regarding the general mechanisms through which a variety of drugs and toxic chemicals damage the kidney.
Authors:
Walter C Prozialeck; Joshua R Edwards
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2012-06-05
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  343     ISSN:  1521-0103     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-17     Completed Date:  2012-11-26     Revised Date:  2013-10-11    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2-12     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA. wprozi@midwestern.edu
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MeSH Terms
Descriptor/Qualifier:
Acute Kidney Injury / chemically induced*,  metabolism*,  pathology
Animals
Apoptosis / drug effects,  physiology
Biological Markers / metabolism
Cadmium / metabolism
Cadmium Poisoning / metabolism*,  pathology
Cell Adhesion / drug effects,  physiology
Environmental Pollutants / toxicity
Humans
Kidney Tubules, Proximal / drug effects*,  metabolism*,  pathology
Grant Support
ID/Acronym/Agency:
R01-ES006478/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Environmental Pollutants; 7440-43-9/Cadmium
Comments/Corrections

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