Abstract
Foothill death camas [Zigadenus paniculatus; or Toxicoscordion paniculatum] is one of about 15 death camas species in North America that is poisonous to grazing livestock. The major toxins in death camas are zygadenine and zygacine, the 3-acetyl ester of zygadenine. However, during plant flower to seed pod growth stages, 3-angeloylzygadenine and 3-veratroylzygadenine become major alkaloids in these reproductive tissues. We hypothesized that 3-angeloylzygadenine, and 3-veratroylzygadenine would be metabolized by esterases in liver, plasma, and rumen to zygadenine. Three death camas alkaloids, zygacine (as a positive control), 3-angeloylzygadenine, and 3-veratroylzygadenine were evaluated with in vitro rumen, plasma and liver S9 incubations. Results from these experiments indicated that 3-veratroylzygadenine was metabolized but not 3-angeloylzygadenine. To confirm the in vitro metabolism results, sheep were orally dosed death camas plant material containing only the reproductive parts of the plants, blood was collected by venipuncture, and alkaloid concentrations measured. The metabolism of 3-veratroylzygadenine but not 3-angeloylzygadenine was confirmed with the in vivo sheep dosing experiments, and we accepted our esterase metabolism hypothesis for 3-veratroylzygadenine.