Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation.
The aim of study was to examine the anti-inflammatory and analgesic effects of adelmidrol, an analogue of palmitoylethanolamide (PEA), in animal models of acute and chronic inflammation [carrageenan-induced paw edema (CAR) and collagen-induced arthritis (CIA)]. In order to elucidate whether the action of adelmidrol is related to activation of peroxisome proliferator-activated receptors (PPAR-α or PPAR-γ), we investigated the effects of PPAR-γ antagonist, GW9662 on adelmidrol mechanism. CAR induced paw edema, hyperalgesia and the activation of pro-inflammatory NF-κB pathway were markedly reduced by treatment with adelmidrol. GW9662, (administered prior to adelmidrol treatment), antagonized the effect of adelmidrol abolishing its positive action. On the contrary, the genetic absence of PPAR-α receptor did not modify the beneficial results of adelmidrol treatment in the acute model of inflammation. In addition, for the first time, we demonstrated that adelmidrol was able to ameliorate both the clinical signs and the histopathology of the joint and the hind paw during chronic inflammation. In particular, the degree of oxidative damage and proinflammatory cytokines and chemokines production were significantly reduced in adelmidrol-treated mice. Moreover, in CIA model, the effect of GW9662 pre-treatment on adelmidrol mechanism was also confirmed. Thus, in this study, we report that adelmidrol reduces the development of acute and chronic inflammation and could represent a novel therapeutic approach for inflammation and pain.
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: dimpellizzeri@unime.it.
Daniela
D
Impellizzeri
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: dipaolar@unime.it.
Rosanna
R
Di Paola
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: mcordaro@alice.it.
Marika
M
Cordaro
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: egugliandolo@me.com.
Enrico
E
Gugliandolo
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: giovy-6@hotmail.it.
Giovanna
G
Casili
Department of Health Sciences, V.le Europa, Campus S. Venuta, Catanzaro, Italy. Electronic address: morittu@unicz.it.
Valeria Maria
VM
Morittu
Department of Health Sciences, V.le Europa, Campus S. Venuta, Catanzaro, Italy. Electronic address: britti@unicz.it.
Domenico
D
Britti
Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy. Electronic address: eesposito@unime.it.
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, School of Medicine, University of Manchester, Manchester, United Kingdom. Electronic address: salvator@unime.it.
Salvatore
S
Cuzzocrea
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000188:drug therapy; D001522:Behavior, Animal; D002351:Carrageenan / Q000633:toxicity; D002908:Chronic Disease / Q000188:drug therapy; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010169:Palmitic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D003998:Dicarboxylic Acids; D010169:Palmitic Acids; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C552602:adelmidrol; D002351:Carrageenan
ALIAmides; Adelmidrol; Cytokines; Inflammation; Mast cells; PPARS