AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (April 5, 2005). doi:10.1152/ajprenal.00038.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/2/F469    most recent
00038.2005v1
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 Li, S.
Right arrow Articles by Portilla, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, S.
Right arrow Articles by Portilla, D.
Submitted on January 28, 2005
Accepted on March 29, 2005

Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF

Shenyang Li1, Neriman Gokden1, Mark D. Okusa2, Renu Bhatt1, and Didier Portilla1*

1 Division of Nephrology, Departments of Internal Medicine and Pathology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare Syatem, Little Rock, AR, USA
2 Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA

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

Recently we demonstrated that Peroxisome proliferator activated receptor-alpha (PPAR{alpha}) ligand ameliorates cisplatin-induced acute renal failure (ARF) by preventing inhibition of substrate oxidation, and also by preventing apoptosis and necrosis of the proximal tubule. In the following studies we examined the protective effect of PPAR{alpha} ligand on cisplatin-induced inflammatory responses during ARF. Mice subjected to a single intraperitoneal injection of cisplatin developed ARF at day 3. Cisplatin increased mRNA and protein expression of TNF{alpha}, RANTES and also up-regulated endothelial adhesion molecules ICAM-1/ VCAM-1, chemokine receptors CCR1/CCR5. Cisplatin also led to neutrophil infiltration in the cortico-medullary region. Pretreatment of wild-type mice with WY-14,643, a fibrate class of PPAR{alpha} ligands, prior to cisplatin significantly suppressed cisplatin-induced up-regulation of cytokine/chemokine expression; prevented neutrophil accumulation and ameliorated renal dysfunction. In contrast, treatment with PPAR{alpha} ligand prior to cisplatin did not prevent cytokine/chemokine production, neutrophil accumulation and did not protect kidney function in PPAR{alpha} null mice. In addition, we observed that cisplatin-induced NF-{kappa}B binding activity in nuclear extracts of wild type mice was markedly reduced by treatment with PPAR{alpha} ligand. These results demonstrate that PPAR{alpha} exerts an anti-inflammatory effect in kidney tissue by a mechanism that include inhibition of NF-{kappa}B DNA binding activity, and this effect results in inhibition of neutrophil infiltration, cytokine/chemokine release, and amelioration of cisplatin-induced acute renal failure.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
J. Luo, T. Tsuji, H. Yasuda, Y. Sun, Y. Fujigaki, and A. Hishida
The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats
Nephrol. Dial. Transplant., July 1, 2008; 23(7): 2198 - 2205.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
N. Kindt, A. Menzebach, M. Van de Wouwer, I. Betz, A. De Vriese, and E. M. Conway
Protective role of the inhibitor of apoptosis protein, survivin, in toxin-induced acute renal failure
FASEB J, February 1, 2008; 22(2): 510 - 521.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. H. Lu, D.-J. Oh, B. Dursun, Z. He, T. S. Hoke, S. Faubel, and C. L. Edelstein
Increased Macrophage Infiltration and Fractalkine Expression in Cisplatin-Induced Acute Renal Failure in Mice
J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 111 - 117.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
Y. Kamijo, K. Hora, K. Kono, K. Takahashi, M. Higuchi, T. Ehara, K. Kiyosawa, H. Shigematsu, F. J. Gonzalez, and T. Aoyama
PPAR{alpha} Protects Proximal Tubular Cells from Acute Fatty Acid Toxicity
J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3089 - 3100.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
L. Baud and E. Letavernier
PPAR{alpha} Contributes to Tubular Protection
J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3017 - 3018.
[Full Text] [PDF]

Home page
 CJASNHome page
S. K. Jo, M. H. Rosner, and M. D. Okusa
Pharmacologic Treatment of Acute Kidney Injury: Why Drugs Haven't Worked and What Is on the Horizon
Clin. J. Am. Soc. Nephrol., March 1, 2007; 2(2): 356 - 365.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
R. A. Zager, A. C. M. Johnson, S. Lund, and J. Randolph-Habecker
Toll-like receptor (TLR4) shedding and depletion: acute proximal tubular cell responses to hypoxic and toxic injury
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F304 - F312.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
H. Boulanger, R. Mansouri, J. F. Gautier, and D. Glotz
Are peroxisome proliferator-activated receptors new therapeutic targets in diabetic and non-diabetic nephropathies?
Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2696 - 2702.
[Full Text] [PDF]

Home page
 Toxicol SciHome page
M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters
The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR)
Toxicol. Sci., April 1, 2006; 90(2): 269 - 295.
[Abstract] [Full Text] [PDF]


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