Couet C E, Hopley J, Hanley A B
Ministry of Agriculture, Fisheries and Food, Central Science Laboratory, Colney, Norwich, UK.
Toxicon. 1996 Sep;34(9):1058-61. doi: 10.1016/0041-0101(96)00056-6.
Two pyrrolizidine alkaloids and one pyrrolizidine alkaloid-N-oxide were incubated with microsomal preparations from humans, rat and avocado and the product profiles examined. The alkaloids were converted to dehydroretronecine, the putative toxic metabolite, by both rat and human microsomal preparations. In addition, alkaloid-N-oxides, the major detoxication products from pyrrolizidine alkaloids, were also formed. The pyrrolizidine alkaloid-N-oxide was converted to both dehydroretronecine and the parent alkaloid. This suggests that the toxicity of pyrrolizidine alkaloid-N-oxides could be greater than suggested hitherto as a result of conversion to the toxic metabolite via the parent alkaloid. Quantitative differences in the proportions of products formed by the different microsomal preparations may be of significance in the extrapolation of toxicological data from animal models such as the rat to humans.
将两种吡咯里西啶生物碱和一种吡咯里西啶生物碱 -N-氧化物与来自人类、大鼠和鳄梨的微粒体制剂一起孵育，并检查产物谱。大鼠和人类微粒体制剂均将这些生物碱转化为假定的有毒代谢物脱氢倒千里光碱。此外，还形成了作为吡咯里西啶生物碱主要解毒产物的生物碱 -N-氧化物。吡咯里西啶生物碱 -N-氧化物转化为脱氢倒千里光碱和母体生物碱。这表明，由于通过母体生物碱转化为有毒代谢物，吡咯里西啶生物碱 -N-氧化物的毒性可能比迄今所认为的更大。不同微粒体制剂形成的产物比例的定量差异在从大鼠等动物模型向人类外推毒理学数据时可能具有重要意义。
