Eastman D F, Dimenna G P, Segall H J
Drug Metab Dispos. 1982 May-Jun;10(3):236-40.
Two macrocyclic 14C-pyrrolizidine alkaloids (PA's), senecionine an seneciphylline, were studied regarding the distribution, excretion, transfer into milk, and covalent binding to hepatic macromolecules in BALB/c mice. After injection, radioactivity was rapidly excreted in the urine and feces (84% or greater) within 16 hr. The liver contained over 1.5% of the dose at 16 hr. A small amount, 0.04%, of the dose was transferred into the milk in 16 hr; the majority of radioactivity was found in the skim-milk fraction, suggesting that the PA's were transferred to the milk as water-soluble metabolites. Both PA's covalently bound to liver macromolecules (DNA, RNA, and protein). The binding to calf thymus DNA and microsomal macromolecules was measured in vitro. The binding was diminished in the absence of O2 or a NADPH-generating system or by boiling the microsomes. No inhibition of the binding by KCN was observed.
研究了两种大环14C-吡咯里西啶生物碱（PA），即千里光碱和叶千里光碱在BALB/c小鼠体内的分布、排泄、向乳汁中的转移以及与肝脏大分子的共价结合情况。注射后，放射性在16小时内迅速经尿液和粪便排出（84%或更多）。16小时时肝脏中含有的剂量超过1.5%。16小时内有少量（0.04%）的剂量转移到乳汁中；大部分放射性存在于脱脂乳部分，这表明PA是以水溶性代谢物的形式转移到乳汁中的。两种PA都与肝脏大分子（DNA、RNA和蛋白质）发生共价结合。在体外测定了它们与小牛胸腺DNA和微粒体大分子的结合情况。在无氧或无NADPH生成系统的情况下，或者通过煮沸微粒体，结合作用会减弱。未观察到KCN对结合的抑制作用。
