Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by ROBERTSON, D. G.
Right arrow Articles by de la IGLESIA, F. A.
Right arrow Search for Related Content
PubMed
Right arrow Articles by ROBERTSON, D. G.
Right arrow Articles by de la IGLESIA, F. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1987 Oxford University Press

research-article

The Pathogenesis of Trimethyltin Chloride-Induced Nephrotoxicity

DONALD G. ROBERTSON*,{dagger}, SANG-NAM KIM{dagger}, ROBERT H. GRAY* and FELIX A. de la IGLESIA*,{dagger}

*Department of Environmental and Industrial Health, School of Public Health, The University of Michigan Ann Arbor, Michigan 48109 {dagger}Department of Pathology and Experimental Toxicology, Warner-Lambert/Parke-Davis Pharmaceutical Research Ann Arbor, Michigan 48105

The Pathogenesis of Trimethyltin Chloride-Induced Nephrotoxicity. Robertson, D. G., KIM, S. N., GRAY, R. H., AND DE LA IGLESIA, F. A. (1987). Fundam. Appl. Toxicol. 8, 147–158. In exploratory studies aimed at elucidating CNS effects due to heavy metal toxicity, signs of compromised renal function were seen in rats. The studies reported here describe the sequential steps of the development of nephrotoxicity by trimethyltin chloride (TMT) in rats. Single doses of 12.25 mg/kg TMT administered orally to 150- to 175-g Long-Evans rats elicited overt signs of toxicity including behavioral abnormalities and marked weight loss. Concurrent with the development of these signs, nephrotoxicity was manifested as functional kidney compromise and associated histopathologic evidence of tubular damage. Pathological changes in the kidneys from treated rats were hyaline droplet inclusions, attenuated brush border, basolateral vacuolization, and eosinophilic granular casts in the proximal tubule cells. These lesions were detected as early as 2 days post-treatment and progressed with time in an orderly and sequential fashion. Renal lesions between 5 and 8 days were mild to severe cortical tubular dilatation, hydropic degeneration, and diffuse hyaline droplet deposition in the lower nephron tubules. Medullary edema and exfoliation of degenerated tubular epithelial cells with cast formation followed from 8 to 11 days. The morphological changes were accompanied by marked elevation of blood urea nitrogen, parallel with polyuria at Day 2 and oliguria by Day 14. Behavioral abnormalities as well as weight loss correlated well with the time course and severity of renal dysfunction and progression of morphological changes. A second experiment compared the effects of TMT in rats of different weights. Heavier rats were more sensitive than lighter rats to the nephrotoxic effects of TMT. These effects were independent of recognizable neurotoxic effects of TMT in the hippocampus.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.