AJP - Renal Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (May 9, 2007). doi:10.1152/ajprenal.00158.2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
293/1/F325    most recent
00158.2007v1
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 Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ramesh, G.
Right arrow Articles by Reeves, W. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ramesh, G.
Right arrow Articles by Reeves, W. B.
Submitted on April 4, 2007
Accepted on May 3, 2007

Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice

Ganesan Ramesh1, Binzhi Zhang1, Satoshi Uematsu2, Shizuo Akira2, and W. Brian Reeves1*

1 Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States
2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Osaka, Japan

* To whom correspondence should be addressed. E-mail: wreeves{at}psu.edu.

A major toxicity of the cancer chemotherapeutic agent cisplatin is acute renal failure. Sepsis is a common cause of acute renal failure in humans and patients who receive cisplatin are at increased risk for sepsis. Accordingly, this study examined the interactions between cisplatin and endotoxin in vivo with respect to renal function and cytokine production. Mice were treated with either a single dose of cisplatin or two doses of LPS administered 24 hours apart, or both agents in combination. Administration of 10 mg/kg cisplatin had no effect on blood urea nitrogen or creatinine levels throughout the course of the study. LPS resulted in a modest rise in blood urea nitrogen at 24 and 48 hours, which returned to normal by 72 hours. In contrast, mice treated with both cisplatin and LPS developed severe renal failure and an increase in mortality. Urine, but not serum, TNF-{alpha} levels showed a synergistic increase by cisplatin and LPS. Urinary IL-6, MCP-1, KC, GM-CSF also showed a synergistic increase with cisplatin+LPS treatment. The renal dysfunction induced by cisplatin+LPS was completely dependent upon TLR4 signaling and partially dependent upon TNF-{alpha} production. Increased cytokine production was associated with a moderate increase in infiltrating leukocytes which was not different between cisplatin+LPS and LPS alone. These results indicate that cisplatin and LPS act synergistically to produce nephrotoxicity which may involve pro-inflammatory cytokine production.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
W. Wang, W. B. Reeves, L. Pays, P. Mehlen, and G. Ramesh
Netrin-1 Overexpression Protects Kidney from Ischemia Reperfusion Injury by Suppressing Apoptosis
Am. J. Pathol., September 1, 2009; 175(3): 1010 - 1018.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. Naito, R. A. Zager, and K. Bomsztyk
BRG1 Increases Transcription of Proinflammatory Genes in Renal Ischemia
J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1787 - 1796.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. Rosen and I. E. Stillman
Acute Tubular Necrosis Is a Syndrome of Physiologic and Pathologic Dissociation
J. Am. Soc. Nephrol., May 1, 2008; 19(5): 871 - 875.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. Zhang, G. Ramesh, S. Uematsu, S. Akira, and W. B. Reeves
TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity
J. Am. Soc. Nephrol., May 1, 2008; 19(5): 923 - 932.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.