Excretion of metabolites in urine and faeces from rats dosed with the heterocyclic amine, 2-amino-9H-pyrido[2,3-b]indole (AαC)
Excretion of metabolites in urine and faeces from rats dosed with the heterocyclic amine, 2-amino-9H-pyrido[2,3-b]indole (AαC)
复制标题
DOI：
10.1016/j.fct.2004.01.011
复制
发表时间：
2004-06-01
影响因子：
4.3
通讯作者：
Frandsen, H
中科院分区：
文献类型：
--
作者：
Frederiksen, H;Frandsen, H
2-氨基- 9h -吡哆[2,3-b]吲哚（AalphaC）是一种在普通烹饪过程中形成的致突变性和致癌性的杂环胺。在模型系统中，α c可以通过热分解色氨酸或动物或植物来源的蛋白质来形成。本研究对α α c在大鼠体内的代谢进行了研究。给大鼠注射标记为AalphaC的氚。在三天内收集尿液和粪便。采用高效液相色谱-质谱法测定α α c代谢产物，液相闪烁计数法测定α α c代谢产物的含量。结合代谢物的特征是酶水解β -葡萄糖醛酸酶或芳基磺化酶。数据显示，所有大鼠的AalphaC代谢模式相似。约55%的剂量在72小时内通过尿液和粪便排出，主要的AalphaC代谢物（31%）在最初的24小时内排出。除了少量未代谢的AalphaC外，还发现了7种共轭代谢物。三种次要代谢物被表征为3-OH-AalphaC和6-OH-AalphaC的α - n -2-葡萄糖醛酸和葡萄糖醛酸偶联物。四种代谢物均以硫酸偶联物为特征，在尿中排泄的代谢物中占最大的量。两个主要的硫酸偶联物被鉴定为α -3- o -硫酸盐和α -6- o -硫酸盐，而次要的硫酸偶联物被认为是其他o -磺化代谢物。在最初的24小时内，粪便中仅排出α - c，约占剂量的12%。在大鼠尿液和粪便中未检测到任何活化的α α c代谢物。在未来，必须研究α α c与DNA和蛋白质等大分子的积累或结合。(C) 2004 Elsevier Ltd.版权所有。
2-amino-9H-pyrido[2,3-b]indole (AalphaC) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems AalphaC can be formed by pyrolysing either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of AalphaC in rats was investigated. Rats were dosed with tritium labelled AalphaC. Urine and faeces were collected over three days. The metabolites of AalphaC were characterised by HPLC-MS and quantified by liquid scintillation counting. Conjugated metabolites were characterised by enzymatic hydrolyses with beta-Glucuronidase or arylsulfatase. The data showed that the metabolic pattern of AalphaC was similar in all rats. About 55% of the dose was excreted in urine and faeces during 72 h and the major amount of AalphaC metabolites (31%) was excreted during the first 24 h. In addition to a small amount of unmetabolised AalphaC seven conjugated metabolites were characterised. Three minor metabolites were characterised as AalphaC-N-2-glucuronide and glucuronic acid conjugates of 3-OH-AalphaC and 6-OH-AalphaC. Four metabolites were all characterised as sulphuric acid conjugates and accounted for the largest amount of metabolites excreted in urine. The two major sulphuric acid conjugates were identified as AalphaC-3-O-sulfate and AalphaC-6-O-sulfate, while the minor sulphuric acid conjugates were proposed to be other O-sulfonated metabolites. In faeces only AalphaC was excreted and accounted for about 12% of dose during the first 24 hours. Any activated metabolites of AalphaC were not detected in rat urine or faeces. In future accumulation or binding of AalphaC to macromolecules such as DNA and proteins has to be studied. (C) 2004 Elsevier Ltd. All rights reserved.