Departamento de Farmacologia, Instituto de Biociências de Botucatu, Unesp - Univ Estadual Paulista, Botucatu, SP, Brasil.
Free Radic Biol Med. 2010 Jun 15;48(12):1636-43. doi: 10.1016/j.freeradbiomed.2010.03.010. Epub 2010 Mar 18.
Apocynin has been widely used as an NADPH oxidase inhibitor in many experimental models. However, concern regarding the efficacy, selectivity, and oxidative side effects of the inhibitor is increasing. In this study, our aim was to characterize the pro-oxidant properties of apocynin and the structurally-related compounds vanillin and vanillic acid. Glutathione (GSH), cysteine, ovalbumin, and the coenzyme NADPH were chosen as potential target biomolecules that could be affected by transient free radicals from apocynin, vanillin and vanillic acid. Additionally, trolox and rifampicin were used as models of hydroquinone moieties, which are particularly susceptible to oxidation. Transient radicals were generated by horseradish peroxidase/hydrogen peroxide-mediated oxidation. In the presence of apocynin, oxidation of GSH was increased seven-fold, and the product of this reaction was identified as GSSG. Similar results were obtained for oxidation of cysteine and ovalbumin. Oxidation of the coenzyme NADPH increased more than 100-fold in the presence of apocynin. Apocynin also caused rapid oxidation of trolox and rifampicin to their quinone derivatives. In conclusion, the pro-oxidant activity of apocynin is related to its previous oxidation leading to transient free radicals. This characteristic may underlie some of the recent findings regarding beneficial or deleterious effects of the phytochemical.
白杨素已被广泛用作许多实验模型中的 NADPH 氧化酶抑制剂。然而，人们对抑制剂的疗效、选择性和氧化副作用的担忧日益增加。在这项研究中，我们的目的是描述白杨素以及结构相关的化合物香草醛和香草酸的促氧化剂特性。谷胱甘肽 (GSH)、半胱氨酸、卵清蛋白和辅酶 NADPH 被选为可能受白杨素、香草醛和香草酸的瞬时自由基影响的潜在靶生物分子。此外，trolox 和利福平被用作对苯二酚部分特别容易氧化的模型。瞬态自由基通过辣根过氧化物酶/过氧化氢介导的氧化产生。在白杨素存在下，GSH 的氧化增加了七倍，并且该反应的产物被鉴定为 GSSG。半胱氨酸和卵清蛋白的氧化也得到了类似的结果。辅酶 NADPH 的氧化在白杨素存在下增加了 100 多倍。白杨素还导致 trolox 和利福平迅速氧化为其醌衍生物。总之，白杨素的促氧化剂活性与其先前的氧化导致的瞬态自由基有关。这一特性可能是最近关于植物化学物质有益或有害影响的一些发现的基础。
