Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 38 (4), 356-66

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

Affiliations

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

Rosanna Di Paola et al. Shock.

Abstract

This study was designed to assess a protective effect of palmitoylethanolamide (PEA) in the development of inflammation after ischemia-reperfusion injury of the kidney. Moreover, to suggest a possible mechanism, renal ischemia-reperfusion was performed in mice with targeted disruption of peroxisome proliferator-activated receptor α (PPAR-α) gene (PPAR-αKO) to explain whether the observed PEA effect was dependent on PPAR-α pathway. Peroxisome proliferator-activated receptor-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 and tubular and reperfusion injury were measured, specifically serum urea, creatinine, aspartate aminotransferase and γ-glutamyl transferase, and creatinine clearance. In addition, renal sections were used for histological scoring of renal injury and for immunologic evidence of nitrotyrosine formation, poly[adenosine diphosphate-ribose] (PAR), and adhesion molecules expression. The oxidative stress-sensitive nuclear factor κB signaling pathway was also investigated by Western blot analysis. Kidney myeloperoxidase activity and malondialdehyde levels were measured for assessment of polymorphonuclear leukocyte cell infiltration and lipid peroxidation, respectively. Apoptotic mechanisms were also investigated. Moreover, the infiltration and activation of mast cells were explored. In vivo, PEA administration during ischemia significantly reduced the increase in (i) creatinine, γ-glutamyl transferase, aspartate aminotransferase; (ii) nuclear translocation of nuclear factor κB p65; (iii) kidney myeloperoxidase activity and malondialdehyde levels; (iv) nitrotyrosine, PAR, and adhesion molecules expression; (v) the infiltration and activation of mast cells; and (vi) apoptosis. Our results clearly demonstrate that PEA significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by ischemia-reperfusion injury. Moreover, the positive effects of PEA were at least in part dependent on PPAR-α pathway.

Similar articles

See all similar articles

Cited by 10 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback