Xenobiotica ( IF 1.3 ) Pub Date : 2018-01-08 , DOI: 10.1080/00498254.2017.1419309 Yan Liu 1 , Ang Li 1 , Xiaoyan Jiang 2 , Xiaosong Zhu 1 , Xiuli Feng 1 , Xiao Sun 1 , Zhongxi Zhao 1, 3, 4
1. Allyl methyl disulfide (AMDS) is one of the main compounds in garlic, whereas its metabolism has not been studied yet.
2. In this work, we first identified the metabolites of AMDS in rat erythrocytes and rats using GC–MS. The transformation mechanism study among different metabolites was then conducted. The apparent kinetics of AMDS in rat erythrocytes and pharmacokinetics of AMDS by oral administration in rats were also studied.
3. The metabolic pathway study showed that AMDS was mainly metabolized in rats to allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2) through mechanisms of reduction, methylation and oxidation. The transformation mechanism study indicated that AMDS was firstly reduced to allyl mercaptan (AM) in rat erythrocytes, and then methylated to allyl methyl sulfide (AMS) by S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and finally oxidized to AMSO and AMSO2 by liver microsomes. The half-life of AMDS in rat erythrocytes was 6.285 ± 0.014 min while the half-lives of its active metabolites AMSO and AMSO2 in vivo were 18.17 and 17.50 h, respectively. Also, the large AUCs of the two active metabolites were observed, indicating potential applications of AMDS for certain pharmacological effects.
中文翻译:
烯丙基甲基二硫化物在大鼠中的代谢和药代动力学研究。
1.烯丙基甲基二硫化物(AMDS)是大蒜中的主要化合物之一,但尚未对其代谢进行研究。
2.在这项工作中,我们首先使用GC-MS鉴定了大鼠红细胞和大鼠中AMDS的代谢产物。然后进行了不同代谢物之间的转化机理研究。还研究了大鼠红细胞中AMDS的表观动力学和大鼠口服AMDS的药代动力学。
3.代谢途径研究表明,AMDS在大鼠中主要通过还原,甲基化和氧化机制代谢为烯丙基甲基亚砜(AMSO)和烯丙基甲基砜(AMSO 2)。转化机制研究表明,AMDS首先在大鼠红细胞中还原为烯丙基硫醇(AM),然后通过S-腺苷甲硫氨酸(SAM)和S-腺苷同型半胱氨酸(SAH)甲基化为烯丙基甲基硫醚(AMS),最后被氧化为AMSO和AMSO 2被肝微粒体吸收。AMDS在大鼠红细胞中的半衰期为6.285±0.014分钟,而其活性代谢产物AMSO和AMSO 2 在体内的半衰期分别为18.17和17.50小时。此外,观察到两种活性代谢物的大AUC,表明AMDS在某些药理作用方面的潜在应用。