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.

中文翻译：

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使用脂质体作为膜模型来评估药物-膜相互作用对依托度酸的抗氧化性能的贡献。

这项工作强调需要将抗氧化剂测定与药物-膜相互作用研究相结合，以更准确地描述非甾体抗炎药（NSAIDs）的抗氧化剂特征。比较了在脂质体和水溶液中进行的不同实验，并将其用于评估依托度酸对脂质过氧化的保护作用。脂质过氧化反应是由源自2,2'-偶氮二（2-ami基丙烷）二盐酸盐（AAPH）的过氧自由基（ROO *）和芬顿反应产生的羟基自由基（HO *）诱导的，并通过三种具有不同亲脂性的荧光探针-荧光素; 十六烷酰基氨基荧光素（HDAF）和二苯基己三烯丙酸（DPHPA）。还通过稳态各向异性测量评估了由于脂质过氧化引起的膜流动性变化。依托度酸与脂质双层的相互作用通过膜ζ电位测量来评估。结果表明药物位于膜表面附近，并表明依托度酸可以清除所研究的自由基，但程度不同，这取决于所测定的培养基和反应性物种。使用不同的探针和脂质体作为膜模拟系统可以使我们得出结论，膜脂过氧化不仅与抗氧化剂的清除特性有关，而且与它们与脂质双层相互作用的能力有关。结果表明药物位于膜表面附近，并表明依托度酸可以清除所研究的自由基，但程度不同，这取决于所测定的培养基和反应性物种。使用不同的探针和脂质体作为膜模拟系统可以使我们得出结论，膜脂过氧化不仅与抗氧化剂的清除特性有关，而且与它们与脂质双层相互作用的能力有关。结果表明药物位于膜表面附近，并表明依托度酸可以清除所研究的自由基，但程度不同，这取决于所测定的培养基和反应性物种。使用不同的探针和脂质体作为膜模拟系统可以使我们得出结论，膜脂过氧化不仅与抗氧化剂的清除特性有关，而且与它们与脂质双层相互作用的能力有关。