Peroxisome Proliferator-Activated Receptor-α Contributes to the Resolution of Inflammation after Renal Ischemia/Reperfusion Injury
| Autor: | Patel, Ns, DI PAOLA, R, Mazzon, E, Britti, D, Thiemermann, C, Cuzzocrea, Salvatore, DI PAOLA, Rosanna |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Agonist medicine.drug_class Ischemia Peroxisome proliferator-activated receptor Inflammation Pharmacology Mice Animals Medicine PPAR alpha chemistry.chemical_classification Kidney Fenofibrate Renal ischemia business.industry medicine.disease Disease Models Animal medicine.anatomical_structure chemistry Reperfusion Injury Anesthesia Molecular Medicine Kidney Diseases medicine.symptom business Reperfusion injury medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 328:635-643 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.108.146191 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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