title: Use of liposomes as membrane models to evaluate the contribution of drug-membrane interactions to antioxidant properties of etodolac.
abstract: This work stresses the need to combine antioxidant assays and drug-membrane interaction studies to describe more accurately the antioxidant profile of non-steroidal anti-inflammatory drugs (NSAIDs). Different experiments performed in liposomes and aqueous solution were compared and used to evaluate the protective effect of etodolac in lipid peroxidation. Lipid peroxidation was induced by the peroxyl radical (ROO*) derived from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydroxyl radical (HO*) generated by the Fenton reaction and was assessed by the fluorescence intensity decay of three fluorescence probes with distinct lipophilic properties--fluorescein; hexadecanoyl aminofluorescein (HDAF) and diphenylhexatriene propionic acid (DPHPA). Membrane fluidity changes due to lipid peroxidation were also evaluated by steady-state anisotropy measurements. Interactions of etodolac with lipid bilayers were evaluated by membrane zeta-potential measurements. Results indicate a drug location near the membrane surface and show that etodolac can scavenge the radicals studied but to a variable extent, depending on the assayed media and reactive species. The use of different probes and liposomes as membrane mimetic systems allowed us to conclude that membrane lipoperoxidation is not only related to the scavenging characteristics of the antioxidants, but also to their ability to interact with lipid bilayers.
authors.affiliation: REQUIMTE, Serviço de Química Física, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. mlucio@ff.up.pt
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Helena
authors.initials: H
authors.lastname: Ferreira
authors.forename: José L F C
authors.initials: JL
authors.lastname: Lima
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D016880:Anisotropy; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D004161:Diphenylhexatriene / Q000031:analogs & derivatives / Q000737:chemistry; D017308:Etodolac / Q000494:pharmacology*; D019793:Fluorescein / Q000737:chemistry; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D016166:Free Radical Scavengers / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D053835:Unilamellar Liposomes / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002839:Chromans; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D053835:Unilamellar Liposomes; D004161:Diphenylhexatriene; D017308:Etodolac; C058719:(hexadecanoyl)aminofluorescein; C037385:1-(4'-carboxyethyl)-6-diphenyl-1,3,5-hexatriene; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D019793:Fluorescein