Tissue Distribution of Radioactivity in Rats given Tritiated Analogues of Hepatotoxic Pyrrolizidine Alkaloids

Abstract

1. [³H]Retronecine 7,9-bis-N-ethylcarbamate (RC) given intravenously (120 mg/kg) to male rats showed similar tissue distribution of radioactivity to that after an equally hepatotoxic dose (40 mg/kg) of [³H]synthanecine A bis-N-ethylcarbamate (SAC), but the ³H in most tissues after ³H-SAC was about double that after ³H-RC.

2. Concentrations of radioactivity were initially highest in liver and lung, but were higher in lung after ³H-RC than after ³H-SAC, reflecting the higher pneumotoxicity of the former. Concentrations of radioactive metabolites strongly attached to liver tissue were approx. the same 1 day after similarly hepatotoxic doses of either compound.

3. Excretion of radioactivity from ³H-RC was about double that from ³H-SAC in urine, and half that in faeces during the first day.