title: Attenuation of experimental TPA-induced dermatitis by acetylenic acetogenins is associated with inhibition of PLA₂ activity.
abstract: Topical application of acetylenic acetogenins (AAG) from avocado (0.01-1.0mg/ear), was effective in inhibiting both 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, and in decreasing tissue myeloperoxidase activity (indicative of polymorphonuclear leukocyte influx). Maximum edema inhibition of 72% was achieved by AAG at lower concentration (0.6 mg/ear) than that of the anti-inflammatory drug indomethacin (2mg/ear). The maximum myeloperoxidase inhibition of 60% was obtained at AAG concentration 0.1mg/ear. Chemical reduction of unsaturated bonds in aliphatic chain of AAG molecules almost abrogated inhibition effect of AAG at high concentration. In vitro AAG administration reduced secretion of PGE(2) in TPA-induced keratinocytes, and inhibited total PLA(2) and sPLA(2) activities in HaCaT cells. The results indicate a topical anti-inflammatory effect of acetylenic acetogenins which is associated with inhibition of PLA(2) activity in skin.
authors: Departamento de Farmacologia, Universidade Federal do Paraná, Centro Politécnico, Curitiba, Brazil.
authors: Michel Fleith
authors: MF
authors: Otuki
authors: Ouri
authors: O
authors: Schwob
authors: Arthur
authors: A
authors: Silveira Prudente
authors: Igor
authors: I
authors: Zaltsman
authors: Shai
authors: S
authors: Meretski
authors: Joseph
authors: J
authors: Segal
authors: Saul
authors: S
authors: Yedgar
authors: Gennady
authors: G
authors: Rosenblat
mesh_terms: D054378:Acetogenins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000114:Acetylene / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000201:enzymology* / Q000209:etiology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects*
chemical_list: D054378:Acetogenins; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; D000114:Acetylene