Feng Yukun, Wang Saide, Wang Hui, Peng Ying, Zheng Jiang
Wuya College of Innovation, Shenyang Pharmaceutical University , Shenyang, Liaoning 110016, People's Republic of China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province and Guizhou Medical University , Guiyang, Guizhou 550004, People's Republic of China.
J Agric Food Chem. 2018 Feb 7;66(5):1258-1263. doi: 10.1021/acs.jafc.7b05186. Epub 2018 Jan 25.
Methyleugenol (ME), a natural ingredient of several herbs and spices used in the human diet, is hepatocarcinogenic in rodents. Following metabolic activation to the reactive carbocation intermediate, ME can bind covalently to DNA, which is directly associated with its carcinogenicity. In this work, a non-invasive approach to determine ME exposure was established by monitoring the urinary N-(methylisoeugenol-3'-yl)-2'-deoxyadenosine (ME-dA) adduct. The developed method entails liquid-liquid extraction enrichment of urinary ME-dA, incorporation of deuterated ME-dA as an internal standard, and analysis by liquid chromatography coupled tandem mass spectrometry. Male rats (10-12 weeks, 180-200 g) were treated (p.o.) with ME, and ME-dA was excreted in urine in a dose- and time-dependent manner. The non-invasive approach enabled us to successfully determine exposure to ME-containing herbs and spices. These results suggest that ME-dA can potentially serve as an effective biomarker of ME exposure in rats. It is expected that the developed approach of detecting urinary ME-dA will facilitate the investigation of ME carcinogenesis.
甲基丁香酚（ME）是人类饮食中使用的多种草药和香料的天然成分，在啮齿动物中具有肝致癌性。在代谢活化为活性碳正离子中间体后，ME可与DNA共价结合，这与其致癌性直接相关。在这项工作中，通过监测尿中N-（甲基异丁香酚-3'-基）-2'-脱氧腺苷（ME-dA）加合物，建立了一种测定ME暴露的非侵入性方法。所开发的方法包括液-液萃取富集尿中的ME-dA，加入氘代ME-dA作为内标，并通过液相色谱-串联质谱法进行分析。雄性大鼠（10-12周龄，180-200克）经口给予ME，ME-dA以剂量和时间依赖性方式从尿中排出。这种非侵入性方法使我们能够成功地测定对含ME的草药和香料的暴露情况。这些结果表明，ME-dA有可能作为大鼠ME暴露的有效生物标志物。预计所开发的检测尿中ME-dA的方法将有助于对ME致癌作用的研究。
