Excretion of the pyrrolizidine alkaloid heliotrine in the urine and bile of sheep

The Journal of Pathology
1969.0

Abstract

Ingestion of certain plants of the families Boraginaceae, Compositae and Leguminosae may be followed by liver damage, which is ascribed to pyrrolizidine alkaloids present in these plants. The hepatotoxicity of pyrrolizidines has been recognised in man as well as in domestic and experimental animals. Hepatotoxic potency varies with different pyrrolizidine alkaloids, and it has not been established whether these individual differences lie in direct cytotoxic action or in the facility with which the alkaloids are converted in vivo to metabolites more or less toxic than the parent compounds. Thus, interest attaches to both how much of a given amount of alkaloid may be excreted and the form in which it is excreted, as both contribute to an understanding of the pharmacodynamics of pyrrolizidine intoxication. In the present work, a study was made of the excretion in the urine and in the bile of the alkaloid heliotrine after it was infused intravenously, or per fistulam into the duodenum. The concentrations of heliotrine and of metabolites containing an unaltered pyrrolizidine ring were followed in these fluids and in blood. Heliotrine is one of five pyrrolizidine alkaloids present in Heliotropium europaeum, a summer-growing weed that is responsible for large numbers of deaths in sheep in parts of south-eastern Australia. It was chosen for the present study since it was available in pure, crystalline form, it has already been studied extensively in toxicity experiments with small animals and its metabolism by rumen micro-organisms and liver microsomal preparations is currently under investigation in this laboratory.

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