|Green, Benedict - Ben|
Submitted to: Poisoning by Plants, Mycotoxins, and Related Toxins
Publication Type: Book / Chapter
Publication Acceptance Date: 5/10/2010
Publication Date: 5/1/2011
Citation: Green, B.T., Welch, K.D., Pfister, J.A., Cook, D., Stegelmeier, B.L., Lee, S.T., Gardner, D.R., Panter, K.E. 2011. The physiological effects and toxicokinetics of tall larkspur (Delphinium barbeyi) alkaloids in cattle. In: Riet-Correa, F., Pfister, J., Schild, A.L., Wierenga, T., editors. Poisoning by Plants, Mycotoxins, and Related Toxins. Cambridge, MA. CAB International. p. 557-65.
Interpretive Summary: Tall Larkspur species found in high mountain pastures are often toxic to cattle and are responsible for significant economic losses to cattle producers. Poisoning of cattle by larkspur (Delphinium spp) has been attributed to the effects of norditerpenoid alkaloids that are produced by the plant and that are present in high concentrations in plant tissues. The purpose of the study reported here was to describe the simple elimination kinetics of MLA and deltaline and evaluate the heart rate response in cattle during a 96-hour period following oral administration of dried ground tall larkspur. Because the clearance of MLA is relatively prolonged, a withdrawal time of 7 days is suggested to allow poisoned animals to eliminate larkspur-associated toxins. Given that serum MLA concentration was correlated with heart rate, development of tachycardia may be an early indicator of poisoning.
Technical Abstract: Norditerpenoid alkaloids of larkspur (Delphinium spp.) have a range of pharmacological and physiological properties. For example, the norditerpenoid alkaloid methyllycaconitine (MLA) can act as competitive antagonist at nicotinic cholinergic receptors. In this study, both dose-response and toxicokinetic experiments were performed in cattle. In the dose-response experiment, cattle received doses of dried finely ground larkspur ranging from 0.5 – 15 mg/kg body weight. Heart rate and external anal sphincter tone were measured at 0 and 24 hours. For the toxicokinetic experiment, cattle were housed in metabolism crates and dosed with 12 mg/kg dried finely ground larkspur, heart rate was continuously monitored and serum samples obtained over 96 hours. In cattle dosed with larkspur, there were dose-related increases in heart rate and decreases in sphincter tone. The Tmax values (maximum serum concentrations) for MLA and deltaline were 8.8 ± 1.2 and 5.0 ± 0.6 hours, respectively. The t1/2 (elimination half life) values for MLA and deltaline were 20.5 ± 4.1 and 8.2 ± 0.6 hours, respectively. These results suggest that the effects of norditerpenoid alkaloids in cattle are dose dependent. Additionally, MLA and deltaline reach maximum serum concentrations by 10 hours and serum MLA, but not deltaline, concentrations are positively correlated with changes in heart rate. These results also demonstrated that in cattle 99% of the serum MLA and deltaline is eliminated by six days post-ingestion.