| In vivo: |
| Chem Biol Interact. 1987;63(1):91-104. | | Metabolism and toxicity of anacrotine, a pyrrolizidine alkaloid, in rats.[Pubmed: 3652286] |
The effects of Anacrotine, a pyrrolizidine alkaloid (PA) which has the structure of senecionine with an additional 6-hydroxy group, have been investigated in weanling male rats.
METHODS AND RESULTS:
When Anacrotine was given i.p. (100 mg/kg), pyrrolic metabolites reached a peak level in the liver during the first 0.5 h, then fell rapidly to a lower level which subsequently declined more slowly. Anacrotine caused acute centrilobular necrosis and congestion of the liver when 125 mg/kg or more was given i.p., but oral doses (up to 180 mg/kg) caused relatively little liver necrosis.In contrast, Anacrotine produced much more severe lung damage than most other pyrrolizidine alkaloids. Hearts showed myocardial necrosis of the right ventricular wall. DehydroAnacrotine, the putative reactive pyrrolic metabolite of Anacrotine, given i.v. to rats, caused dose-related chronic lung and heart damage identical to that produced by Anacrotine, but after lower doses (6-27 mg/kg); larger amounts caused acute lung damage.
CONCLUSIONS:
It is suggested that the severe lung damage in animals given Anacrotine is due to dehydroAnacrotine, formed in the liver. |
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