Peroxisome proliferator-activated receptor-α contributes to the resolution of inflammation after renal ischemia/reperfusion injury

N. S A Patel, Rosanna Di Paola, Emanuela Mazzon, Domenico Britti, Christoph Thiemermann, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

This study was designed to elucidate the role of peroxisome proliferator-activated receptor (PPAR)-α in the development of inflammation after ischemia/reperfusion injury of the kidney. We have evaluated the effects of ischemia/reperfusion on renal dysfunction, injury, and inflammation in wild-type mice or mice in which the gene for PPAR-α has been deleted [PPAR-α(-/-)] and then treated with the PPAR-α agonist fenofibrate. Mice were subjected to bilateral renal ischemia (30 min) and reperfusion (24 h) and received fenofibrate (3 mg/kg i.p.) before reperfusion. Plasma creatinine, urea, and aspartate aminotransferase were all used as indicators of renal dysfunction and injury. Kidneys were used for histological and immunohistochemical analysis and markers of inflammation. Fenofibrate significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by ischemia/reperfusion injury. The degree of renal dysfunction, injury, and inflammation caused by ischemia/reperfusion was also significantly augmented in PPAR-α(-/-) mice compared with their wild-type littermates. It is interesting that fenofibrate did not protect PPAR-α(-/-) mice against ischemia/reperfusion injury. Therefore, we propose that ligands of PPAR-α may be useful in the treatment of renal ischemia/reperfusion injury and that endogenous PPAR-α limits the degree of renal dysfunction, injury, and inflammation associated with ischemia/reperfusion injury.

Original languageEnglish
Pages (from-to)635-643
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume328
Issue number2
DOIs
Publication statusPublished - Feb 2009

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Peroxisome Proliferator-Activated Receptors
Reperfusion Injury
Inflammation
Kidney
Fenofibrate
Reperfusion
Wounds and Injuries
Ischemia
Aspartate Aminotransferases
Urea
Creatinine
Ligands

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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Peroxisome proliferator-activated receptor-α contributes to the resolution of inflammation after renal ischemia/reperfusion injury. / Patel, N. S A; Di Paola, Rosanna; Mazzon, Emanuela; Britti, Domenico; Thiemermann, Christoph; Cuzzocrea, Salvatore.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 328, No. 2, 02.2009, p. 635-643.

Research output: Contribution to journalArticle

Patel, N. S A ; Di Paola, Rosanna ; Mazzon, Emanuela ; Britti, Domenico ; Thiemermann, Christoph ; Cuzzocrea, Salvatore. / Peroxisome proliferator-activated receptor-α contributes to the resolution of inflammation after renal ischemia/reperfusion injury. In: Journal of Pharmacology and Experimental Therapeutics. 2009 ; Vol. 328, No. 2. pp. 635-643.
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