Endotoxin and Cisplatin Synergistically Induce Renal Dysfunction and Cytokine Production in Mice.
From: Division of Nephrology, Pennsylvania State College of Medicine, 500 Univ. Dr., Hershey, PA 17033, USA.
American journal of physiology. Renal physiology
- Publish Date: Jul 2007
- ISSN: 0363-6127
- Volume: 293
- Issue: 1
- Pages: F325-32
- Medium: Print
- Language: English
- Citation (JAMA): Ramesh Ganesan, Zhang Binzhi, Uematsu Satoshi, et al. Endotoxin and Cisplatin Synergistically Induce Renal Dysfunction and Cytokine Production in Mice.. Am. J. Physiol. Renal Physiol. Jul 2007;293:F325-32
Abstract
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 h 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 h, which returned to normal by 72 h. 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, and GM-CSF also showed a synergistic increase with cisplatin+LPS treatment. The renal dysfunction induced by cisplatin+LPS was completely dependent on TLR4 signaling and partially dependent on 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 proinflammatory cytokine production.
Mesh Headings (Keywords): Animals, Antineoplastic Agents, Blood Urea Nitrogen, Chemokines, Cisplatin, Creatinine, Cytokines, Endotoxins, Immunohistochemistry, Kidney, Kidney Failure, Acute, Kidney Function Tests, Male, Mice, Mice, Inbred C57BL, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Toll-Like Receptor 4, Tumor Necrosis Factor-alpha
Check for Full Text / PubMed Unique Identifier (PMID): 17494092
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.