Studies in the toxicity and metabolism of bitterweed (Hymenoxys odorata DC.)

Abstract

The toxicity of hymenoxon and hymenolane, two of the sesquiterpene lactone components of bitterweed, was evaluated by a single-administration oral toxicity test in sheep (the target species), with three dosage levels of each of the following materials: hymenoxon with hymenolane, hymenoxon alone, and whole bitterweed. The toxic response was evaluated according to lethality and histopathology in those sheep that died, and by levels of selected serum components and loss of body weight in survivors. It was determined that acute intoxication caused by whole bitterweed is qualitatively indistinguishable from intoxication caused by hymenoxon. In particular, hymenolane exhibited no synergistic effect on the acute oral toxicity of hymenoxon. In all three treatments, lethality was associated with high levels of hymenoxon. These results suggest that hymenoxon is the only toxic principle of significance in bitterweed. A 48-h single-dose oral LD50 of approximately 75 mg/kg was determined for hymenoxon in the sheep. In immature hamsters, biweekly oral administration of hymenoxon at several dosage levels for two months produced weight loss, depression and histopathologic lesions (acute and subacute) similar to those observed in sheep intoxicated with bitterweed/hymenoxon. In spite of the hamster's relative resistance to hymenoxon--the acute oral LD50 was calculated to be 620 mg/kg--the hamster was found to be an acceptable laboratory animal model for ovine hymenoxon intoxication. Basal activities of hepatic microsomal aniline hydroxylase were compared in sheep previously determined to be either bitterweed-susceptible or bitterweed-resistant, and no significant difference was found between the susceptible and the resistant sheep. This study suggests that the cytochrome P(,450)-dependent mixed-function oxidase system does not have a central role in the metabolic detoxification of hymenoxon. ...