Santos Fernando, Teixeira Lígia, Lúcio Marlene, Ferreira Helena, Gaspar Diana, Lima José L F C, Reis Salette
REQUIMTE, Departamento de Química Física, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Free Radic Res. 2008 Jul;42(7):639-50. doi: 10.1080/10715760802270326.
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.
非甾体抗炎药（NSAIDs）通过抑制环氧化酶（COX）来治疗炎症过程。然而，它们对脂质过氧化的作用可能是COX抑制的替代途径。由于炎症和脂质过氧化是细胞表面现象，因此研究了NSAIDs对膜模型的影响。过氧化由2,2'-偶氮二异丁基脒二盐酸盐（AAPH）产生的过氧自由基（ROO*）诱导，并使用具有不同亲脂性的荧光探针在水性或脂质介质中进行评估：荧光素；HDAF和DPH-PA。测试了舒林酸及其代谢物的抗氧化作用，并将其与它们的膜相互作用相关联。药物-膜相互作用包括以下研究：通过荧光猝灭确定药物位置；通过ζ电位测量研究药物与膜表面的相互作用；以及通过稳态各向异性研究膜流动性变化。结果表明，活性NSAID（舒林酸硫化物）穿透脂质双层并保护膜免受氧自由基的侵害。非活性形式（舒林酸和舒林酸砜）与膜的相互作用较弱，并且在水性介质中是更好的自由基清除剂。
