Peroxisome proliferator-activated receptor-alpha contributes to the resolution of inflammation after renal ischemia/reperfusion injury.
This study was designed to elucidate the role of peroxisome proliferator-activated receptor (PPAR)-alpha 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-alpha has been deleted [PPAR-alpha(-/-)] and then treated with the PPAR-alpha 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-alpha(-/-) mice compared with their wild-type littermates. It is interesting that fenofibrate did not protect PPAR-alpha(-/-) mice against ischemia/reperfusion injury. Therefore, we propose that ligands of PPAR-alpha may be useful in the treatment of renal ischemia/reperfusion injury and that endogenous PPAR-alpha limits the degree of renal dysfunction, injury, and inflammation associated with ischemia/reperfusion injury.
Patel
Nimesh S A
NS
Centre for Translational Medicine and Nephrology, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary-University of London, Charterhouse Square, London, United Kingdom. n.s.patel@qmul.ac.uk
di Paola
Rosanna
R
Mazzon
Emanuela
E
Britti
Domenico
D
Thiemermann
Christoph
C
Cuzzocrea
Salvatore
S
D000818:Animals; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D051379:Mice; D047493:PPAR alpha / Q000502:physiology*; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology
D047493:PPAR alpha