Institute of Applied Biosciences, Chair of Food Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Mol Nutr Food Res. 2011 Jul;55(7):1079-86. doi: 10.1002/mnfr.201000487. Epub 2011 Feb 23.
Monohydroxylation of alternariol (AOH) and alternariol-9-methyl ether (AME) has previously been reported as a prominent metabolic route under cell-free conditions. This pathway gives rise to several catechol metabolites and may therefore be of toxicological relevance.
To clarify whether hydroxylation of AOH and AME occurs under in vivo-like conditions in the presence of conjugation reactions, the metabolism of the Alternaria toxins has now been studied in precision-cut rat liver slices. Four catechol metabolites of AOH and two of AME, together with several of their O-methylation products, as catalyzed by catechol-O-methyl transferase, were clearly identified after incubation of the liver slices with AOH and AME. These metabolites were predominantly present as conjugates with glucuronic acid and/or sulfate. In preliminary studies with bile duct-cannulated male rats dosed with AOH by gavage, the four monohydroxylated metabolites of AOH could also be demonstrated in the bile either as catechols or as O-methyl ethers.
These experiments clearly show that AOH and AME undergo catechol formation in vivo and warrant closer examination of the toxicological significance of this metabolic pathway.
先前的研究表明，在无细胞条件下，链格孢酚（AOH）和链格孢酚-9-甲醚（AME）的单羟化作用是一种主要的代谢途径。该途径会产生几种儿茶酚代谢物，因此可能具有毒理学意义。
为了阐明在存在结合反应的情况下，AOH 和 AME 的羟化作用是否在类似于体内的条件下发生，现在已经在大鼠肝切片中研究了这些真菌毒素的代谢情况。在将 AOH 和 AME 孵育到肝切片中后，明显鉴定出 AOH 和 AME 的四种儿茶酚代谢物以及儿茶酚-O-甲基转移酶催化的两种 AME 的代谢物，以及它们的几种 O-甲基化产物。这些代谢物主要以与葡萄糖醛酸和/或硫酸盐的结合物形式存在。在对经胆管插管的雄性大鼠进行 AOH 灌胃给药的初步研究中，也可以在胆汁中检测到 AOH 的四种单羟化代谢物，其形式可以是儿茶酚或 O-甲基醚。
这些实验清楚地表明 AOH 和 AME 在体内会形成儿茶酚，有必要更仔细地研究这种代谢途径的毒理学意义。
