Location: Poisonous Plant Research
Title: Effect of MDL-Type alkaloids on tall larkspur toxicosis Authors
Submitted to: Poisoning by Plants, Mycotoxins, and Related Toxins
Publication Type: Book / Chapter
Publication Acceptance Date: January 29, 2010
Publication Date: N/A
Interpretive Summary: Current management recommendations for grazing cattle on larkspur-infested ranges are based primarily on the concentration of MSAL-type alkaloids. Delphinium barbeyi is one of the more problematic species of tall larkspur plants due to its high concentration of MLA. However, the most abundant norditerpenoid alkaloids in most D. barbeyi populations are the less toxic MDL-type alkaloids, either deltaline or 14-OAD. Previous research using a mouse model, demonstrated that the MDL-type alkaloids have an additive affect on the toxicity of MLA. In this study, experiments were performed to determine if MDL-type alkaloids affect the overall toxicity of tall larkspur plants in cattle. The research from this study demonstrates that MSAL-type alkaloids such as MLA cause greater toxicity than MDL-type alkaloids and are the primary factors responsible for the toxicity of larkspur plants. Consequently, for a larkspur plant to be toxic to livestock, a sufficient quantity of MSAL-type alkaloids is required. However, MDL-type alkaloids appear to potentiate the overall toxicity of the MSAL-type alkaloids and should be considered when predicting potential toxicity of larkspur populations. Consequently when chemical analyses are performed on larkspur plants to assess their toxic potential, the concentration of both the MSAL-type and total alkaloids should be determined, with more weight given to the MSAL-type alkaloids.
Technical Abstract: Larkspur plants contain numerous norditerpenoid alkaloids which include the 7, 8-methylenedioxylycoctonine (MDL) -type alkaloids and the N-(methylsuccinimido) anthranoyllycoctonine (MSAL) -type alkaloids. The MSAL-type alkaloids are generally much more toxic (typically > 20x) than the MDL-type alkaloids. Toxicity of many tall larkspurs has been attributed to the high concentration of MSAL-type alkaloids including methyllycaconitine (MLA). However, the norditerpenoid alkaloids found in highest concentrations in most D. barbeyi and D. occidentale populations are either deltaline or 14-O-acetyldictyocarpine (14-OAD), both less toxic MDL-type alkaloids. Although the individual toxicities of MLA, 14-OAD, and deltaline have been determined, the impact (additive or antagonistic) that large concentrations of deltaline or 14-OAD in the plant have on the toxicity of tall larkspurs is unknown. The effect of MDL-type alkaloids on the toxicity of MLA were compared using LD50 from mice receiving i.v. administration of these alkaloids individually or in combination at ratios of: 1:1, 1:5, and 1:25, MLA : MDL-type alkaloids. The LD50 for MLA alone was 4.4 ± 0.7 mg/kg BW, whereas the co-administration of MLA and deltaline at 1:1, 1:5, and 1:25 resulted in an LD50 of 2.7, 2.5, and 1.9 mg/kg BW, respectively. Similarly, the co-administration of MLA and 14-OAD at 1:1, 1:5, and 1:25 resulted in an LD50 of 3.1, 2.2, and 1.5 mg/kg BW, respectively. Cattle were dosed with different populations of tall larkspur that contain different ratios of MDL- to MSAL-type alkaloids. Three different populations of tall larkspur were used, a D. barbeyi population with a ratio of 3.1:1.0 MDL- to MSAL-type alkaloids, another D. barbeyi population with a 1:1 ratio, and a D. glaucescens population with a 0.6:1.0 ratio. The dose, based on the MSAL-type alkaloid concentration, required for each plant population to elicit similar clinical signs of poisoning in cattle was determined. As the ratio of MDL- to MSAL-type alkaloids in the plant material decreased, the amount of MSAL-type alkaloids required to elicit clinical signs increased approximately 2 fold. The results from this study indicate that less toxic MDL-type alkaloids in tall larkspur exacerbate the toxicity of the plant. Consequently both the amount of MSAL-type alkaloids and the amount of total (MSAL + MDL) alkaloids should be fully characterized to more accurately determine the relative toxicity of tall larkspur plant material.