Shan Zhen, Yu Qingfeng, Purwaha Preeti, Guo Bin, Qian Steven Y
Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, ND 58105, USA.
Free Radic Res. 2009 Jan;43(1):13-27. doi: 10.1080/10715760802567606.
Increased evidence from animal and in vitro cellular research indicates that the metabolism of eicosapentaenoic acid (EPA) can inhibit carcinogenesis in many cancers. Free radical-mediated peroxidation is one of many possible mechanisms to which EPA's anti-cancer activity has been attributed. However, no direct evidence has been obtained for the formation of any EPA-derived radicals. In this study, a combination of LC/ESR and LC/MS was used with alpha-[4-pyridyl 1-oxide]-N-tert-butyl nitrone to identify the carbon-centred radicals that are formed in lipoxygenase-catalysed EPA peroxidation. Of the numerous EPA-derived radicals observed, the major products were those stemming from beta-scission of 5-, 15- and 18-EPA-alkoxyl radicals. By means of an internal standard in LC/MS, this study also quantified each radical adduct in all its redox forms, including an ESR-active form and two ESR-silent forms. The comprehensive profile of EPA's radical formation provides a starting point for ongoing research in defining the biological effects of radicals generated from EPA peroxidation.
越来越多来自动物和体外细胞研究的证据表明，二十碳五烯酸（EPA）的代谢可以抑制多种癌症的致癌作用。自由基介导的过氧化是EPA抗癌活性的众多可能机制之一。然而，尚未获得任何EPA衍生自由基形成的直接证据。在本研究中，将LC/ESR和LC/MS与α-[4-吡啶基1-氧化物]-N-叔丁基硝酮结合使用，以鉴定在脂氧合酶催化的EPA过氧化过程中形成的碳中心自由基。在观察到的众多EPA衍生自由基中，主要产物是那些源于5-、15-和18-EPA-烷氧基自由基β-断裂的产物。通过LC/MS中的内标，本研究还对所有氧化还原形式的每种自由基加合物进行了定量，包括ESR活性形式和两种ESR沉默形式。EPA自由基形成的全面概况为正在进行的研究提供了一个起点，以确定EPA过氧化产生的自由基的生物学效应。
