Interactions of sulindac and its metabolites with phospholipid membranes: An explanation for the peroxidation protective effect of the bioactive metabolite

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Fernando Santos (Autor) Outra; Ligia Teixeira (Autor) Outra; Marlene Lucio (Autor) FFUP; Helena Ferreira (Autor) Outra; Diana Gaspar (Autor) Outra; Jose L F C Lima (Autor) FFUP; Salette Reis (Autor) FFUP

Revista

Título: Free Radical Research

Vol. 42

Páginas: 639-650

ISSN: 1071-5762

Editora: Taylor & Francis

Indexação

ISI Web of Knowledge - 11 Citações

ISI Web of Science

Scopus - 14 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

CORDIS: Ciências da Saúde

Outras Informações

ID Authenticus: P-004-39E

DOI: 10.1080/10715760802270326

Resumo (PT): Non-steroidal anti-inflammatory drugs (NSAIDs) treat inflammatory processes by inhibition of cycloxygenase (COX). However, their action against lipid peroxidation can be an alternative pathway to COX inhibition. Since inflammation and lipid peroxidation are cell-surface phenomena, the effects of NSAIDs on membrane models were investigated. Peroxidation was induced by peroxyl radical (ROO•) derived from AAPH and assessed in aqueous or lipid media using fluorescence probes with distinct lipophilic properties: fluorescein; HDAF and DPH-PA. The antioxidant effect of Sulindac and its metabolites was tested and related with their membrane interactions. Drug-membrane interactions included the study of: drug location by fluorescence quenching; drug interaction with membrane surface by zeta-potential measurements; and membrane fluidity changes by steady-state anisotropy. Results revealed that the active NSAID (sulindac sulphide) penetrates into the lipid bilayer and protects the membrane against oxy-radicals. The inactive forms (sulindac and sulindac sulphone) present weaker interactions with the membrane and are better radical scavengers in aqueous media <br> <br> Keywords: AAPH fluorescence Lipid peroxidation liposome non-steroidal anti-inflammatory drugs (NSAIDs) peroxyl radical <br> <a target="_blank" href="http://web.ebscohost.com/ehost/detail?vid=3&hid=8&sid=7262047d-a5b5-405f-b485-cb92dc0d0766%40sessionmgr4&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d"> Texto integral</a> <br> <br>

Abstract (EN): Non-steroidal anti-inflammatory drugs (NSAIDs) treat inflammatory processes by inhibition of cycloxygenase (COX). However, their action against lipid peroxidation can be an alternative pathway to COX inhibition. Since inflammation and lipid peroxidation are cell-surface phenomena, the effects of NSAIDs on membrane models were investigated. Peroxidation was induced by peroxyl radical (ROO) derived from AAPH and assessed in aqueous or lipid media using fluorescence probes with distinct lipophilic properties: fluorescein; HDAF and DPH-PA. The antioxidant effect of Sulindac and its metabolites was tested and related with their membrane interactions. Drug-membrane interactions included the study of: drug location by fluorescence quenching; drug interaction with membrane surface by zeta-potential measurements; and membrane fluidity changes by steady-state anisotropy. Results revealed that the active NSAID (sulindac sulphide) penetrates into the lipid bilayer and protects the membrane against oxy-radicals. The inactive forms (sulindac and sulindac sulphone) present weaker interactions with the membrane and are better radical scavengers in aqueous media.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12