COVALENT BINDING OF 2 PYRROLIZIDINE ALKALOIDS, SENECIONINE AND SENECIPHYLLINE, TO HEPATIC MACROMOLECULES AND THEIR DISTRIBUTION, EXCRETION, AND TRANSFER INTO MILK OF LACTATING MICE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (3) , 236-240
Abstract
Two macrocyclic 14C-pyrrolizidine alkaloids (PA), senecionine and seneciphylline, were studied regarding the distribution, excretion, transfer into milk, and covalent binding to hepatic macromolecules in BALB/c mice. After i.p. injection, radioactivity was rapidly excreted in the urine and feces (.gtoreq. 84%) within 16 h. The liver contained > 1.5% of the dose at 16 h. A small amount, 0.04%, of the dose was transferred into the milk in 16 h; the majority of radioactivity was found in the skim-milk fraction, suggesting that the PA was transferred to the milk as water-soluble metabolites. Both PA 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.

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