Abstract | BACKGROUND: METHODS: Rats were pretreated with LPS (1 mg/kg, IP, 24 hours prior to ischemia) in the absence (control) or presence of the selective PPARgamma antagonist GW9662 (1 mg/kg, IP, 24 and 12 hours prior to ischemia). Twenty-four hours after injection of LPS, rats were subjected to 60 minutes of bilateral renal ischemia, followed by 6 hours of reperfusion. Serum and urinary indicators of renal injury and dysfunction were measured, specifically serum creatinine, aspartate aminotransferase, and gamma-glutamyl- transferase, creatinine clearance, urine flow, and fractional excretion of sodium. Kidney PPARgamma1 mRNA levels were determined by reverse transcriptase-polymerase chain reaction. RESULTS: Pretreatment with LPS significantly attenuated all markers of renal injury and dysfunction caused by I/R. Most notably, GW9662 abolished the protective effects of LPS. Additionally, I/R caused an up-regulation of kidney PPARgamma1 mRNA levels compared to sham animals, which were unchanged in rats pretreated with LPS. CONCLUSION: We document here for the first time that endogenous ligands of PPARgamma may contribute to the protection against renal I/R injury afforded by LPS pretreatment in the rat.
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Authors | Massimo Collino, Nimesh S A Patel, Kevin M Lawrence, Marika Collin, David S Latchman, Muhammad M Yaqoob, Christoph Thiemermann |
Journal | Kidney international
(Kidney Int)
Vol. 68
Issue 2
Pg. 529-36
(Aug 2005)
ISSN: 0085-2538 [Print] United States |
PMID | 16014029
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2-chloro-5-nitrobenzanilide
- Anilides
- Lipopolysaccharides
- PPAR gamma
- RNA, Messenger
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Topics |
- Anilides
(pharmacology)
- Animals
- Drug Interactions
- Kidney Diseases
(drug therapy, physiopathology)
- Lipopolysaccharides
(pharmacology)
- Male
- PPAR gamma
(antagonists & inhibitors, genetics)
- RNA, Messenger
(analysis)
- Rats
- Rats, Wistar
- Reperfusion Injury
(drug therapy, physiopathology)
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