Mutagenic and toxicologic implications of pyrrolizidine (Senecio) alkaloids Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/bv73c449c

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  • The Salmonella/mammalian-microsome mutagenicity test was used to evaluate Senecio jacobaea (SJ) plant, Pyrrolizidine alkaloids (PA) and metabolites in goat milk, to evaluate response differences with microsomes from several animal species and to compare SJ plant responses to other plants. Bioassessment experiments were conducted to evaluate PA toxicity changes associated with copper (Cu) and molybdenum (Mo) ingestion in sheep and esterase inhibition, microsomal enzyme induction and cysteine supplement in rats. Acetone extracts of SJ caused negative or toxic mutagenic responses in the absence of liver microsomes and positive responses after microsomal activation. Senecio PA and monocrotaline gave only negative responses. Milk from SJ-fed goats produced positive mutagenic responses after microsomal activation. Only slight species microsomal differences were observed. Acetone extracts from alfalfa, lettuce and thread-leaf groundsel gave only negative mutagenic responses. Comfrey extracts produced toxic responses that were abolished by the microsomal system. Bracken produced a positive response after bioactivation with liver microsomes. The dietary addition of Cu or Cu and Mo to SJ diets fed to lambs caused only marginal effects on LiverCu levels and no anparenthemolvtic effects. Lambs died after eating about 100% of their body weight in dried SJ with lambs fed the SJ+Cu+Mo diet dying about four wks before lambs fed the SJ+Cu diet. Dietary exposure to esterase inhibiting organophosphates and carbamate resulted in increased PA toxicity. Increased toxicity was demonstrated by decreased PA (Senecio longilobus) LD₅₀ values after dietary exposure to organophosphates (coumaphos, tri-o-cresyl phosphate and malathion) or the carbamate (carbaryl). Rats fed a SJ diet with tri-o-cresyl phosphate (TOCP) had decreased (P<.05) weight gain while rats fed a SJ diet with 2-pyridine aldoxime methiodide (2-PAM) had similar weight gain to those fed just the SJ diet. Rats fed SJ, SJ+ TOCP or SJ+2-PAM diets had similar survival times (approx 60d). Induction of microsomal enzymes by phenobarbital (PB) or dietary eucalyptus leaves caused only marginal effects on the acute LD₅₀ for a PA (Senecio longilobus) mixture. Dietary phenothiazine (PT) did not alter SJ toxicity but did cause reduced feed intake and weight gain. Rats fed SJ with cysteine had increased (P<.05) survival time and SJ ingestion and slightly increased weight gain. Rats fed SJ+cysteine+ PT had increased (P<.05) survival time over SJ and SJ+PT groups with a slight decrease in survival time compared to the SJ+cysteine group.
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