title: Ultramicronized palmitoylethanolamide (PEA-um(®)) in the treatment of idiopathic pulmonary fibrosis.
abstract: Pulmonary fibrosis is a chronic condition characterized by progressive scarring of lung parenchyma. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (PEA-um(®)), an endogenous fatty acid amide, in mice subjected to idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis was induced in male mice by a single intratracheal administration of saline with bleomycin sulphate (1mg/kg body weight) in a volume of 100μL. PEA-um(®) was injected intraperitoneally at 1, 3 or 10mg/kg 1h after bleomycin instillation and daily thereafter. Animals were sacrificed after 7 and 21days by pentobarbitone overdose. One cohort of mice was sacrificed after seven days of bleomycin administration, followed by bronchoalveloar lavage and determination of myeloperoxidase activity, lung edema and histopathology features. In the 21-day cohort, mortality was assessed daily, and surviving mice were sacrificed followed by the above analyses together with immunohistochemical localization of CD8, tumor necrosis factor-α, CD4, interleukin-1β, transforming growth factor-β, inducible nitric oxide synthase and basic fibroblast growth factor. Compared to bleomycin-treated mice, animals that received also PEA-um(®) (3 or 10mg/kg) had significantly decreased weight loss, mortality, inflammation, lung damage at the histological level, and lung fibrosis at 7 and 21days. PEA-um(®) (1mg/kg) did not significantly inhibit the inflammation response and lung fibrosis. This study demonstrates that PEA-um(®) (3 and 10mg/kg) reduces the extent of lung inflammation in a mouse model of idiopathic pulmonary fibrosis.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fusco
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Siracusa
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Crupi
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy; Department of Pharmacological and Physiological Science, Saint Louis University, Saint Louis, MO, USA. Electronic address: salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000577:Amides; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010169:Palmitic Acids / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors; D015431:Weight Loss
chemical_list: D000577:Amides; D015415:Biomarkers; D004983:Ethanolamines; D018836:Inflammation Mediators; D010169:Palmitic Acids; D001761:Bleomycin; C005958:palmidrol
keywords: Disease; Idiopathic pulmonary fibrosis; Lung; Mice; Palmitoylethanolamide