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 KOECHEL, D. A.
Right arrow Articles by RIDGEWELL, R. E.
Right arrow Search for Related Content
PubMed
Right arrow Articles by KOECHEL, D. A.
Right arrow Articles by RIDGEWELL, R. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1991 Oxford University Press

other

The Acute Effects of S-(1,2-Dichlorovinyl)-L-cysteine and Related Chemicals on Renal Function andUltrastructure in the Pentobarbital-Anesthetized Dog: Structure-Activity Relationships, Biotransformation, and Unique Site-Specific Nephrotoxicity1

DANIEL A. KOECHEL2, MARK E. KREJCI and RICHARD E. RIDGEWELL3

Department of Pharmacology, Medical College of Ohio P.O. Box 10008, Toledo, Ohio 43699-0008

Received June 18, 1990; accepted January 15, 1991

The Acute Effects of S-(l,2-Dichlorovinyl}-L-cysteine and Related Chemicals on Renal Function and Ultrastructure in the Pentobarbital-Anesthetized Dog: Structure-Activity Relationships, Biotransformation, and Unique Site-Specific Nephrotoxicity. KOECHEL, D. A., KREJCI, M. E., AND RIDGEWELL, R. E. (1991). Fundam Appl. Toxicol. 17, 17-33. S-(l,2-Dichlorovinyl)-L-cysteine (L-DCVC), a substrate for the renal cysteine conjugate ß-lyase, and other related chemicals were administered intravenously to pentobarbital-anesthetized dogs. Six pertinent findings emerged regarding their nephrotoxicity. (1) L-DCVC was acutely nephrotoxic in the dog. (2) The earliest indicator of L-DCVC-induced renal damage was an increase in the urinary excretion rate of protein. (3) Contrary to results from other species, L-DCVC induced renal ultrastructural lesions only in the S1, and S2 cells of the proximal tubule. (4) The toxicity of L-DCVC (23.15 µmol/kg, iv) to S1 and S2 cells resulted from a direct tubular insult and not from overlapping episodes of hypoxia or ischemia. (5) L-DCVC could be detected in plasma only during the first 30 min after its injection. In addition, no L-DCVC and only small amounts of N-acetyl-L-DCVC and S-(1,2-dichlorovinyl)mercaptoacetic acid (DCV-MAA) (1.5% and <1% of the administered dose, respectively) were detectable in urine during the 6 hr following L-DCVC administration. (6) DCV-MAA and chloroacetic acid as well as other compounds that are not substrates for the renal cysteine conjugate ß3-lyase (i.e., S-allyl-L-cysteine, vinthionine, and S-(l,2-dichlorovinyl)-D,L-a-methylcysteine) were not acutely nephrotoxic. These findings provide indirect evidence for the involvement of ß-lyase in the toxification of L-DCVC in the dog. 1991 Society of Toxicology.


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.