ABSTRACT: This study was designed to assess a protective effect of palmitoylethanolamide (PEA) in the development of inflammation after ischemia/reperfusion injury (IRI) of the kidney. Moreover, in order to suggest a possible mechanism, renal I/R was performed in mice with targeted disruption of PPAR-α gene (PPAR-αKO) to explain whether the observed PEA effect was dependent with PPAR-α pathway.PPAR-αKO and littermate wild-type controls (PPAR-αWT) were subjected to bilateral renal artery occlusion (30 min) and reperfusion (6 h) and received PEA (10 mg/kg i.p.) 15 min before release of clamps. Serum and urinary indicators of renal dysfunction, tubular and reperfusion injury were measured, specifically, serum urea, creatinine, aspartate aminotransferase (AST) and γ-glutamyl transferase (GT), and creatinine clearance. In addition, renal sections were used for histologic scoring of renal injury and for immunologic evidence of nitrotyrosine formation, poly [adenosine diphosphate (ADP)-ribose] (PAR), and adhesion molecules expression. The oxidative stress-sensitive NF-κB signaling pathway was also investigated by western blot analysis. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Apoptotic mechanisms were also investigated. Moreover, the infiltration and activation of mast cells (MCs) were explored. In vivo, PEA administration during ischemia significantly reduced: the increase in (1) creatinine, γGT, AST, (2) nuclear translocation of NF-κBp65; (3) kidney MPO activity and MDA levels, (4) nitrotyrosine, PAR and adhesion molecules expression, (5) the infiltration and activation of MCs and (6) apoptosis. Our results clearly demonstrate that PEA significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by IRI. Moreover, the positive effects of PEA were at least in part dependent with PPAR-α pathway.

Palmitoylethanolamide Reduces Early Renal Dysfunction and Injury Caused by Experimental Ischemia and Reperfusion in Mice.

R. Di Paola;IMPELLIZZERI, DANIELA;MONDELLO, PATRIZIA;ALOISI, Carmela;ESPOSITO, EMANUELA;CUZZOCREA, Salvatore
2012

Abstract

ABSTRACT: This study was designed to assess a protective effect of palmitoylethanolamide (PEA) in the development of inflammation after ischemia/reperfusion injury (IRI) of the kidney. Moreover, in order to suggest a possible mechanism, renal I/R was performed in mice with targeted disruption of PPAR-α gene (PPAR-αKO) to explain whether the observed PEA effect was dependent with PPAR-α pathway.PPAR-αKO and littermate wild-type controls (PPAR-αWT) were subjected to bilateral renal artery occlusion (30 min) and reperfusion (6 h) and received PEA (10 mg/kg i.p.) 15 min before release of clamps. Serum and urinary indicators of renal dysfunction, tubular and reperfusion injury were measured, specifically, serum urea, creatinine, aspartate aminotransferase (AST) and γ-glutamyl transferase (GT), and creatinine clearance. In addition, renal sections were used for histologic scoring of renal injury and for immunologic evidence of nitrotyrosine formation, poly [adenosine diphosphate (ADP)-ribose] (PAR), and adhesion molecules expression. The oxidative stress-sensitive NF-κB signaling pathway was also investigated by western blot analysis. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Apoptotic mechanisms were also investigated. Moreover, the infiltration and activation of mast cells (MCs) were explored. In vivo, PEA administration during ischemia significantly reduced: the increase in (1) creatinine, γGT, AST, (2) nuclear translocation of NF-κBp65; (3) kidney MPO activity and MDA levels, (4) nitrotyrosine, PAR and adhesion molecules expression, (5) the infiltration and activation of MCs and (6) apoptosis. Our results clearly demonstrate that PEA significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by IRI. Moreover, the positive effects of PEA were at least in part dependent with PPAR-α pathway.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11570/2274223
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