title: Adelmidrol, a palmitoylethanolamide analogue, reduces chronic inflammation in a carrageenin-granuloma model in rats.
abstract: Palmitoylethanolamide (PEA) and some of its analogues have shown great efficacy in the treatment of pain and inflammation. Adelmidrol - the International Nonproprietary Name (INN) of the di-amide derivative of azelaic acid - is one of these analogues. The anti-inflammatory and analgesic effects of PEA and adelmidrol are hypothesized to be mediated, at least in part, by mast cell down-modulation. Mast cell mediators released at early stage of the inflammatory process drive the inflammatory reaction to chronicity as it happens in X-carrageenin-induced granulomatous tissue formation. In the present study, the choice of testing adelmidrol depends upon the physicochemical properties of the compound, i.e. the amphipatic feature, that make it more easily soluble than PEA. In this study, we investigated the effect of adelmidrol on granuloma formation induced by lambda-carrageenin-soaked sponge implant in rats. Our results show that the local administration of the compound under study significantly decreases weight and neo-angiogenesis in granulomatous tissue. The anti-inflammatory effect was due to the modulation of mast cells degranulation, as shown by histological analysis and by the inhibition of the release of several pro-inflammatory and pro-angiogenic enzymes (e.g. iNOS, chymase and metalloproteinase MMP-9), and mediators (e.g. nitric oxide and TNF-alpha). The results indicate that adelmidrol, given locally, may represent a potential therapeutic tool in controlling chronic inflammation.
authors.affiliation: Università"Federico II", Napoles, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: De Filippis
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Amico
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cinelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Teresa
authors.initials: T
authors.lastname: Iuvone
mesh_terms: D000577:Amides; D000818:Animals; D015153:Blotting, Western; D002351:Carrageenan; D002452:Cell Count; D002908:Chronic Disease; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004983:Ethanolamines; D006099:Granuloma / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010169:Palmitic Acids / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000577:Amides; D003998:Dicarboxylic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D009573:Nitrites; D010169:Palmitic Acids; D014409:Tumor Necrosis Factor-alpha; C552602:adelmidrol; C005958:palmidrol; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II