AJP - Renal Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (September 19, 2006). doi:10.1152/ajprenal.00517.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/5/F1090    most recent
00517.2005v1
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 Wang, W.
Right arrow Articles by Schrier, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, W.
Right arrow Articles by Schrier, R. W.
Submitted on December 27, 2005
Accepted on May 9, 2006

Pentoxifylline Protects Against Endotoxin-induced Acute Renal Failure in Mice

Wei Wang1, Einath Zolty1, Sandor Falk1, Veena Basava1, Leonid Reznikov1, and Robert W. Schrier1*

1 Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, United States

* To whom correspondence should be addressed. E-mail: robert.schrier{at}uchsc.edu.

Acute renal failure (ARF) in septic patients drastically increases the mortality to 50-80%. Sepsis induces several proinflammatory cytokines including tumor necrosis factor-{alpha} (TNF-{alpha}), a major pathogenetic factor in septic ARF. Pentoxifylline has several functions including downregulation of TNF-{alpha} and endothelia-dependent vascular relaxation. We hypothesized that pentoxifylline may afford renal protection during endotoxemia either by downregulating TNF-{alpha} and/or by improving endothelial function. In wild type mice pentoxifylline protected against the fall in GFR (105.2 ± 6.6 vs 50.2 ± 6.6µl/min, p<0.01) at 16 hours of LPS administration (2.5mg/kg, i.p.). This renal protective effect of pentoxifylline was associated with an inhibition of the rise in serum TNF-{alpha} (1.00±0.55 vs 7.02 ± 2.40pg/ml, p<0.05) and serum IL-1{beta} (31.3 ± 3.6 vs 53.3 ± 5.9 pg/ml, p<0.01) induced by LPS. Pentoxifylline also reversed the LPS-related increase in renal iNOS and ICAM-1 and rise in serum NO. Enhanced RBC deformability by pentoxifylline may have increased shear rate and upregulated eNOS. Studies were therefore performed in eNOS ko mice. The renal protection against endotoxemia with pentoxifylline was again observed as assessed by GFR (119.8 ± 18.0 vs 44.5 ± 16.2 µl/min, p<0.05) and RBF (0.86 ± 0.08 vs 0.59 ± 0.05 ml/min, p<0.05). Renal vascular resistance significantly decreased with the pentoxifylline (91.0 ± 5.8 vs 178.0 ± 7.6mmHg/ml/min, p<0.01). Thus pentoxifylline, an FDA approved drug, protects against endotoxemia-related ARF and involves a decrease in serum TNF-{alpha}, IL-1{beta} and NO as well as a decrease in renal iNOS and ICAM-1.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
W. Wang, S. Bansal, S. Falk, D. Ljubanovic, and R. Schrier
Ghrelin protects mice against endotoxemia-induced acute kidney injury
Am J Physiol Renal Physiol, October 1, 2009; 297(4): F1032 - F1037.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
J A Leithead, J W Ferguson, C M Bates, J S Davidson, A Lee, A J Bathgate, P C Hayes, and K J Simpson
The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure
Gut, March 1, 2009; 58(3): 443 - 449.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
Z. Zhou, P. Gengaro, W. Wang, X.-q. Wang, C. Li, S. Faubel, C. Rivard, and R. W. Schrier
Role of NF-{kappa}B and PI 3-kinase/Akt in TNF-{alpha}-induced cytotoxicity in microvascular endothelial cells
Am J Physiol Renal Physiol, October 1, 2008; 295(4): F932 - F941.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
W. Wang, E. Zolty, S. Falk, S. Summer, Z. Zhou, P. Gengaro, S. Faubel, N. Alp, K. Channon, and R. Schrier
Endotoxemia-related acute kidney injury in transgenic mice with endothelial overexpression of GTP cyclohydrolase-1
Am J Physiol Renal Physiol, March 1, 2008; 294(3): F571 - F576.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
W. Wang, E. Zolty, S. Falk, S. Summer, R. Stearman, M. Geraci, and R. Schrier
Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice
Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1131 - F1136.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
A. Mitra, S. Bansal, W. Wang, S. Falk, E. Zolty, and R. W. Schrier
Erythropoietin ameliorates renal dysfunction during endotoxaemia
Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2349 - 2353.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
G. Ramesh, B. Zhang, S. Uematsu, S. Akira, and W. B. Reeves
Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F325 - F332.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
C. Schmidt, K. Hocherl, F. Schweda, A. Kurtz, and M. Bucher
Regulation of Renal Sodium Transporters during Severe Inflammation
J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1072 - 1083.
[Abstract] [Full Text] [PDF]


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