title: Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats.
abstract: Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Campolo
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Tremolada
authors.affiliation: Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Maestroni
authors.affiliation: Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bandello
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zerbini
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, USA. Electronic address: salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D057167:Claudins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003930:Diabetic Retinopathy / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D057167:Claudins; D016207:Cytokines; D004983:Ethanolamines; D010169:Palmitic Acids; C569044:Tjp1 protein, rat; D042461:Vascular Endothelial Growth Factor A; D062826:Zonula Occludens-1 Protein; D018799:Intercellular Adhesion Molecule-1; C005958:palmidrol
keywords: Diabetic retinopathy; Inflammation; Palmitoylethanolamide; Streptozotocin