Mattocks A R, Legg R F, Jukes R
Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
Toxicol Lett. 1990 Nov;54(1):93-9. doi: 10.1016/0378-4274(90)90060-y.
It has been shown that a short-lived pyrrolic metabolite in fluid flowing out of isolated rat liver perfused with the pyrrolizidine alkaloid, monocrotaline, could be trapped by covalent reaction with a bed of immobilized thiol (thiol-sepharose). Larger amounts of other pyrrolic metabolites, also in the fluid, were not trapped. This provided the first direct support for the widely held hypothesis that reactive pyrrolizidine alkaloid metabolites (dehydro-alkaloids) escape from the liver to damage the lungs of rats in vivo. The relatively smaller proportion of pyrrolic metabolite from retrorsine which could be trapped in this way was consistent with the known lack of pneumotoxicity of this alkaloid. The procedure described should be suitable for trapping other types of electrophilic metabolites.
业已表明，在用吡咯里西啶生物碱单猪屎豆碱灌注的离体大鼠肝脏流出的液体中，一种短寿命的吡咯代谢产物可通过与固定化硫醇（硫醇-琼脂糖）床的共价反应被捕获。液体中大量的其他吡咯代谢产物则未被捕获。这为广泛持有的假说提供了首个直接支持，即具有反应性的吡咯里西啶生物碱代谢产物（脱氢生物碱）从肝脏逸出，在体内损害大鼠的肺部。以这种方式能够捕获的来自倒千里光碱的吡咯代谢产物比例相对较小，这与该生物碱已知缺乏肺毒性是一致的。所描述的方法应适用于捕获其他类型的亲电代谢产物。
