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      Agonists of Peroxisome-Proliferator Activated Receptor-Gamma Reduce Renal Ischemia/Reperfusion Injury

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          Background/Aims: Recent evidence indicates that peroxisome-proliferator activated receptor (PPAR) agonists protect against ischemia/reperfusion (I/R) injury. Here we investigate the effects of the PPAR-γ agonists, rosiglitazone and ciglitazone, on the renal dysfunction and injury caused by I/R of the rat kidney in vivo. Methods: Rosiglitazone or ciglitazone were administered to male Wistar rats prior to and during reperfusion. Biochemical indicators of renal dysfunction and injury were measured and histological scoring of kidney sections was used to assess renal injury. Expression of PPAR isoforms and intercellular adhesion molecule-1 during renal I/R were assessed using RT-PCR and Northern blot, respectively. Myeloperoxidase activity and activation of poly(ADP-ribose) polymerase (PARP) were used as indicators of polymorphonuclear (PMN) cell infiltration and oxidative stress, respectively. Results: Expression of PPAR-α, PPAR-β and PPAR-γ1 (but not PPAR-γ2) was observed in kidneys with down-regulation of PPAR-α expression during renal I/R. Rosiglitazone and ciglitazone significantly reduced biochemical and histological signs of renal dysfunction and injury. Renal expression of ICAM-1 caused by I/R was reduced by rosiglitazone and ciglitazone which was reflected by decreased PMN infiltration into reperfused renal tissues. Both rosiglitazone and ciglitazone reduced PARP activation indicating a reduction of oxidative stress. Conclusion: These results suggest that the PPAR-γ agonists rosiglitazone and ciglitazone reduce the renal dysfunction and injury associated with I/R of the kidney. We propose that one mechanism underlying the protective effects involves inhibition of the expression of ICAM-1, a reduction of PMN infiltration into renal tissues and subsequent reduction of oxidative stress.

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          Most cited references 10

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          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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              The PPARs:  From Orphan Receptors to Drug Discovery†


                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                August 2003
                31 July 2003
                : 23
                : 4
                : 267-276
                aDepartment of Experimental Medicine and Nephrology, William Harvey Research Institute, Queen Mary – University of London, UK; bDepartment of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Japan; cDepartments of Pathology and Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK; dLaboratory of Pharmacology, Faculty of Pharmacy, University of Lisbon, Portugal; eDepartment of Clinical and Experimental Medicine and Pharmacology, Institute of Pharmacology, School of Medicine, University of Messina, Messina, Italy
                72088 Am J Nephrol 2003;23:267–276
                © 2003 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 37, Pages: 10
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                Original Article: Basic Sciences


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