ARS | Publication request: The Effect of High Deltaline Concentration on the Toxicity of Methyllycaconitine in Mice

Submitted to: International Society on Toxicology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: March 1, 2008
Publication Date: March 15, 2008
Citation: Welch, K.D., Panter, K.E., Gardner, D.R., Green, B.T., Pfister, J.A., Cook, D. 2008. The Effect of High Deltaline Concentration on the Toxicity of Methyllycaconitine in Mice. International Society on Toxicology Meeting.

Technical Abstract: Larkspurs (Delphinium) are one of the most serious toxic plant problems on foothill and mountain rangelands in the western U.S. Total costs to the livestock industry have been estimated at over $20 million annually. Larkspur plants contain numerous norditerpenoid alkaloids (>18) which occur as one of two types, MDL-type including deltaline and lycoctonine, and the MSAL-type including methyllycaconitine (MLA) and 14-deacetylnudicauline (14-DAN). The MSAL-type is much more toxic (typically >20x). Currently management recommendations for planning grazing schemes are based primarily on MSAL alkaloid concentrations in larkspurs. Delphinium barbeyi is one of the more problematic species of tall larkspur plants due to its high concentration of MLA and 14-DAN. However, the most abundant norditerpenoid alkaloid in most D. barbeyi populations is either deltaline or 14-acetyldictyocarpine (14-ADV), less toxic MDL alkaloids. Although the toxicity of MLA, 14-DAN, 14-ADC, and deltaline has been individually determined, it is not known what synergistic or antagonistic effects the large concentration of deltaline or 14-ADC in the plant has on the toxicity of MLA. Therefore, it is critical to understand what contributions MDL alkaloids have on the overall toxicity of larkspurs. The effect of deltaline on the toxicity of MLA was assessed by comparing the LD50 of these alkaloids administered individually to Swiss-Webster mice versus the co-administration of these alkaloids at three different rations, 1:1, 1:5, and 1:25 MLA to deltaline. The LD50 for MLA alone was 40.0 ± 0.3 mg / kg B.W. and the LD50 for deltaline alone was 113.3 ± 6.4 mg / kg B.W. The co-administration of MLA and deltaline at 1:1 resulted in an LD50 of 2.7 ± 0.3 mg / kg B.W. The LD50 for the 1:5 group was 2.5 ± 0.2 mg / kg B.W. and the LD50 for the 1:25 group was 1.9 ± 0.1 mg / kg B.W. These results suggest that deltaline has an additive effect on the toxicity of MLA in mice and potentially plays an important role in the overall toxicity of tall larkspur plants in cattle.