Toxic actions of senaetnine, a new pyrrolizidine-type alkaloid, in rats

Senaetnine is a new type of Senecio alkaloid with a dihydropyrrolizinone structure. A limited amount of the crude alkaloid was available for preliminary toxicity tests in weanling male rats via i.p., oral and i.v. routes. Single i.p. or p.o. doses up to 280 mg/kg were not acutely toxic, and showed no evidence of hepatotoxicity. The compound or its metabolites appeared to be eliminated rapidly via the kidneys. However, senaetnine had a direct irritant action on tissues near to the site of i.p. administration, and caused damage to pulmonary vascular tissue when given i.v. Senaetnine is closely related to, but less reactive than, dehydrosenecionine, a putative short-lived metabolite of the alkaloid senecionine. It possesses mild alkylating reactivity, and the evidence indicates that it can cause moderate tissue injury without the need for metabolic activation. This suggests the need for testing of this and related compounds for chronic toxicity and carcinogenicity.