The anti-inflammatory effects of palmitoylethanolamide (PEA) on endotoxin-induced uveitis in rats.
The aim of this study was to investigate the effects of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs), in rats subjected to endotoxin-induced uveitis (EIU). EIU was induced in male rats by a single footpad injection of 200μg lipopolysaccharide (LPS). PEA was administered intraperitoneally at 1h before and 7h after injection of LPS. Another group of animals was treated with vehicle. Dexamethasone (DEX) was administered as a positive control. Rats were sacrificed 16h after injection and the eyes tissues were collected for histology, immunohistochemical and western blot analyses. The histological evaluation of the iris-ciliary body showed an increase of neutrophilic infiltration and nuclear modification of vessel of endothelial cells. PEA treatment decreased the inflammatory cell infiltration and improved histological damage of eye tissues. In addition, PEA treatment reduced pro-inflammatory tumor necrosis factor (TNF-α) levels, protein extravasion and lipid peroxidation. Immunohistochemical analysis for intracellular adhesion molecule (ICAM)-1 and nitrotyrosine showed a positive staining from LPS-injected rats. The degree of staining for ICAM-1 and nitrotyrosine was significantly reduced in eye sections from LPS-injected rats treated with PEA. In addition, an increase of inducible nitric oxide synthase (iNOS) and nuclear factor (NF-κB) was also evaluated in inflammed ocular tissues by western blot. PEA strongly inhibited iNOS expression and nuclear NF-κB translocation. Thus, in this study we demonstrated that PEA reduces the degree of ocular inflammation in a rat model of EIU.
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Daniela
D
Impellizzeri
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Akbar
A
Ahmad
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Giuseppe
G
Bruschetta
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Rosanna
R
Di Paola
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Rosalia
R
Crupi
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Irene
I
Paterniti
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Emanuela
E
Esposito
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy; Manchester Biomedical Research Centre, Manchester Royal Infirmary, University of Manchester, UK. Electronic address: salvator@unime.it.
Salvatore
S
Cuzzocrea
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004983:Ethanolamines / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010169:Palmitic Acids / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014602:Uvea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D000577:Amides; D000893:Anti-Inflammatory Agents; D004983:Ethanolamines; C090509:Icam1 protein, mouse; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010169:Palmitic Acids; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C005958:palmidrol; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
Cytokines; Inflammation; N-palmitoylethanolamide (PEA); Neutrophils; Oxidative stress; Uveitis