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

• Type: Article in International Scientific Journal
• Date: 2008

Authors

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

Journal

Title: Free Radical Research

Vol. 42

Pages: 639-650

ISSN: 1071-5762

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 11 Citations

ISI Web of Science

Scopus - 14 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

CORDIS: Health sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12