马兜铃酸 I 和 II 的代谢研究。

Studies on the metabolism of aristolochic acids I and II.

Krumbiegel G, Hallensleben J, Mennicke W H, Rittmann N, Roth H J

Dr Madaus GmbH & Co., Department of Biochemistry, Cologne, Germany.

Xenobiotica. 1987 Aug;17(8):981-91. doi: 10.3109/00498258709044197.

Abstract

After oral administration of aristolochic acid I (AAI) and aristolochic acid II (AAII) to rats, the following metabolites were isolated from the urine and their structures elucidated: aristolactam I, aristolactam Ia, aristolochic acid Ia, aristolic acid I and 3,4-methylenedioxy-8-hydroxy-1-phenanthrenecarboxylic acid (metabolites of AAI); or aristolactam Ia, aristolactam II and 3,4-methylenedioxy-1-phenanthrenecarboxylic acid (metabolites of AAII). A further metabolite of AAII having a lactam structure has not yet been isolated in pure form. 2. The metabolic pathways have been elucidated by administration of various metabolites. 3. The principal metabolite of AAI in rats was aristolactam Ia; 46% of the dose was excreted in the urine in form of this metabolite and 37% in the faeces. The other substances were minor metabolites. Those metabolites of AAII whose structures have been elucidated were minor metabolites; the largest proportion consisted of aristolactam II, which accounted for 4.6% in the urine and 8.9% in the faeces. 4. The mouse was the only animal which had the same metabolite patterns of AAI and AAII as those found in the rat. Not all the metabolites listed above were found in urine from guinea pigs, rabbits, dogs and man.

摘要

给大鼠口服马兜铃酸I（AAI）和马兜铃酸II（AAII）后，从尿液中分离出以下代谢产物并阐明了其结构：马兜铃内酰胺I、马兜铃内酰胺Ia、马兜铃酸Ia、马兜铃酸I和3,4 - 亚甲二氧基 - 8 - 羟基 - 1 - 菲羧酸（AAI的代谢产物）；或马兜铃内酰胺Ia、马兜铃内酰胺II和3,4 - 亚甲二氧基 - 1 - 菲羧酸（AAII的代谢产物）。尚未以纯形式分离出具有内酰胺结构的AAII的另一种代谢产物。2. 通过给予各种代谢产物阐明了代谢途径。3. AAI在大鼠体内的主要代谢产物是马兜铃内酰胺Ia；46%的剂量以该代谢产物的形式经尿液排出，37%经粪便排出。其他物质是次要代谢产物。已阐明结构的AAII的那些代谢产物是次要代谢产物；其中最大比例的是马兜铃内酰胺II，其在尿液中占4.6%，在粪便中占8.9%。4. 小鼠是唯一具有与大鼠中发现的AAI和AAII相同代谢产物模式的动物。豚鼠、兔子、狗和人的尿液中并未发现上述所有代谢产物。