A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse
A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse
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DOI：
10.1021/tx0600402
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发表时间：
2006-06-19
影响因子：
4.1
通讯作者：
Gonzalez, Frank J.
中科院分区：
文献类型：
--
作者：
Giri, Sarbani;Idle, Jeffrey R.;Gonzalez, Frank J.
槟榔生物碱包括槟榔碱、槟榔定、古瓦胆碱和古瓦辛。大约有6亿槟榔产品使用者，例如嚼槟榔的人，接触到这些生物碱，主要是槟榔碱和槟榔碱。槟榔碱（20 mg/kg p.o.和i. p.）和槟榔碱（20 mg/kg p.o.和i. p.）使用代谢组学方法，采用超高效液相色谱-飞行时间质谱法分析尿液，在小鼠中进行了研究。槟榔碱的代谢产物共鉴定出11种，包括槟榔碱、槟榔碱N-氧化物、槟榔碱N-氧化物、N-甲基哌啶甲酸、N-甲基哌啶酰甘氨酸、槟榔碱酰甘氨酸、槟榔碱酰甘油、槟榔碱巯基尿酸、槟榔碱巯基尿酸和槟榔碱N-氧化物巯基尿酸，以及9种未鉴定的代谢产物。槟榔碱与槟榔碱共有六种代谢产物。槟榔碱给药后0-12小时尿液中排泄的剂量中，原型槟榔碱占0.3- 0.4%，槟榔定占7.1- 13.1%，槟榔碱N-氧化物占7.4- 19.0%，N-甲基哌啶甲酸占13.5-30.3%。槟榔碱给药后0-12 h尿中排泄的槟榔碱和N-甲基哌啶甲酸分别占给药剂量的15.1- 23.0%和14.8%-37.7%。槟榔碱和槟榔定的主要代谢产物N-甲基哌啶甲酸是一种新的碳-碳双键还原代谢产物。另一个不寻常的代谢产物是槟榔碱的单酰基甘油酯。这些不常见的代谢物在槟榔碱和槟榔碱的毒理学中所起的作用（如果有的话）尚不清楚。然而，槟榔碱和槟榔碱代谢转化的深入了解，有助于槟榔生物碱的临床毒理学研究。
The areca alkaloids comprise arecoline, arecaidine, guvacoline, and guvacine. Approximately 600 million users of areca nut products, for example, betel quid chewers, are exposed to these alkaloids, principally arecoline and arecaidine. Metabolism of arecoline (20 mg/kg p.o. and i.p.) and arecaidine (20 mg/kg p.o. and i.p.) was investigated in the mouse using a metabolomic approach employing ultra-performance liquid chromatography-time-of-flight mass spectrometric analysis of urines. Eleven metabolites of arecoline were identified, including arecaidine, arecoline N-oxide, arecaidine N-oxide, N-methylnipecotic acid, N-methylnipecotylglycine, arecaidinylglycine, arecaidinylglycerol, arecaidine mercapturic acid, arecoline mercapturic acid, and arecoline N-oxide mercapturic acid, together with nine unidentified metabolites. Arecaidine shared six of these metabolites with arecoline. Unchanged arecoline comprised 0.3-0.4%, arecaidine 7.1-13.1%, arecoline N-oxide 7.4-19.0%, and N-methylnipecotic acid 13.5-30.3% of the dose excreted in 0-12 h urine after arecoline administration. Unchanged arecaidine comprised 15.1-23.0%, and N-methylnipecotic acid 14.8%-37.7% of the dose excreted in 0-12 h urine after arecaidine administration. The major metabolite of both arecoline and arecaidine, N-methylnipecotic acid, is a novel metabolite arising from carbon-carbon double-bond reduction. Another unusual metabolite found was the monoacylglyceride of arecaidine. What role, if any, that is played by these uncommon metabolites in the toxicology of arecoline and arecaidine is not known. However, the enhanced understanding of the metabolic transformation of arecoline and arecaidine should contribute to further research into the clinical toxicology of the areca alkaloids.