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Abstract

Objective—To compare the toxic effects of a Delphinium occidentale chemotype containing N-(methylsuccinimido) anthranoyllycoctonine (MSAL)—type alkaloids and a D occidentale chemotype lacking MSAL-type alkaloids in mice and cattle.

Animals—225 male Swiss Webster mice and 11 Black Angus steers.

Procedures—4 collections of larkspur containing MSAL-type alkaloids and 4 collections of larkspur lacking MSAL-type alkaloids were used. From each collection, total alkaloid extracts (0.05 to 0.20 mL) were administered via tail-vein injection in 27 to 29 mice. Dried, finely ground plant material from 1 collection with and 1 collection without MSAL-type alkaloids (doses equivalent to 37.6 mg of total alkaloids/kg) were each administered to 8 cattle via oral gavage in a crossover experiment; 3 cattle received a single dose equivalent to 150.4 mg of total alkaloids/kg (no MSAL-type alkaloids). In mice, clinical effects were monitored; in cattle, heart rate was monitored before (baseline) and 24 hours after treatment. At the 24-hour time point, cattle were exercised as a measure of muscle weakness.

Results—In mice, mean LD50 associated with alkaloid extracts prepared from plants that did or did not contain MSAL-type alkaloids was 2.3 and 54.2 mg/kg, respectively. In cattle at 24 hours after treatment, plant material containing MSAL-type alkaloids significantly increased heart rate from baseline and was associated with exercise-induced collapse; plant material lacking MSAL-type alkaloids had no similar effects.

Conclusions and Clinical Relevance—Taxonomic classification of D occidentale alone was not a good indicator of the toxic risk to grazing cattle.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the toxicokinetics of N-(methylsuccinimido)anthranoyllycoctonine–type low larkspur alkaloids in beef cattle.

Animals—5 Black Angus steers and 35 Swiss Webster mice.

Procedures—Low larkspur (Delphinium andersonii) was collected, dried, ground, and administered to 5 steers via oral gavage to provide a dose of 12 mg of N-(methylsuccinimido)-anthranoyllycoctonine alkaloids/kg. Steers were housed in metabolism crates for 96 hours following larkspur administration; heart rate was monitored continuously, and blood samples were collected periodically for analysis of serum concentrations of 16-deacetylgeyerline, methyllycaconitine, geyerline, and nudicauline and assessment of kinetic parameters. The LD50 of a total alkaloid extract from D andersonii was determined in Swiss Webster mice.

Results—The alkaloids were quickly absorbed, with a maximum serum concentration achieved within 18 hours after administration. Geyerline and nudicauline coeluted as 1 peak and were considered together for toxicokinetic analysis. Mean ± SD elimination half-life was 18.4 ± 4.4 hours, 15.6 ± 1.5 hours, and 16.5 ± 5.1 hours for 16-deacetylgeyerline, methyllycaconitine, and geyerline and nudicauline, respectively. There were significant differences in maximum serum concentration, amount absorbed, and distribution half-life among the 4 alkaloids. The mouse LD50 was 9.8 mg/kg.

Conclusions and Clinical Relevance—Results suggested that clinical poisoning was likely to be most severe approximately 18 hours after exposure. Cattle should be closely monitored for at least 36 hours after initial exposure. Additionally, a withdrawal time of approximately 7 days would be required to clear > 99% of the toxic alkaloids from the serum of cattle that have ingested low larkspur.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether larkspur-derived N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids alter heart rate and electrically evoked electromyographic (eEMG) response of the external anal sphincter (EAS) in cattle and whether these effects can be reversed by acetylcholinesterase inhibitors.

Animals—12 beef heifers and 4 cows.

Procedures—3 or 4 heifers were used in 1 or 2 of 7 dose-response experiments; heart rate and EAS eEMG response were assessed before and 24 hours after oral treatment with larkspur (doses equivalent to 0.5 to 15 mg of MSAL-type alkaloids/kg). In 3 subsequent experiments, 3 heifers (1 of which was replaced with another heifer in the control experiment) each received 10 mg of MSAL-type alkaloids/kg and were injected IV with physostigmine (0.04 mg/kg), neostigmine (0.04 mg/kg), or saline (0.9% NaCl) solution 24 hours later, prior to assessment. Additionally, EAS eEMG response was measured in 4 cows before and after epidural administration of 2% lidocaine hydrochloride.

Results—Larkspur-treated heifers developed dose-related increases in heart rate and decreases in EAS eEMG response. Twenty-four hours after administration of MSAL-type alkaloids, neostigmine decreased heart rate but did not affect eEMG response, whereas physostigmine did not affect heart rate but caused a 2-fold increase in eEMG response. In cows, epidural anesthesia did not alter eEMG response, suggesting that transdermal stimulation of the EAS pudendal innervation did not occur.

Conclusions and Clinical Relevance—In cattle, cardiac effects and muscle weakness or loss of EAS eEMG response induced by larkspur-derived MSAL-type alkaloids were reversed by neostigmine or physostigmine, respectively. Treatment with anticholinesterase inhibitors may alter the clinical effects of larkspur poisoning in cattle.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To describe the simple elimination kinetics of methyllycaconitine (MLA) and deltaline and evaluate the heart rate response in cattle following oral administration of larkspur.

Animals—5 healthy Angus steers that were habituated to metabolism crates.

Procedures—Tall larkspur (Delphinium barbeyi) in the early flowering stage was collected, dried, and ground. Each steer received a single dose of larkspur that was equivalent to 10.4 mg of MLA/kg and 11.0 mg of deltaline/kg via oral administration. Steers were housed in metabolism crates during a 96-hour period following larkspur administration; heart rate was monitored continuously, and blood samples were collected periodically for analysis of serum MLA and deltaline concentrations as well as assessment of pharmacokinetic parameters.

Results—No overt clinical signs of poisoning developed in any steer during the experiment. Mean ± SE heart rate reached a maximum of 79.0 ± 5.0 beats/min at 17 hours after larkspur administration. Serum MLA concentration was correlated directly with heart rate. Mean times to maximal serum concentration of MLA and deltaline were 8.8 ± 1.2 hours and 5.0 ± 0.6 hours, respectively. Mean elimination half-life values for MLA and deltaline were 20.5 ± 4.1 hours and 8.2 ± 0.6 hours, respectively.

Conclusions and Clinical Relevance—Following larkspur administration in 5 healthy steers, maximum serum concentrations of MLA and deltaline were detected within 10 hours, and changes in serum MLA concentration and heart rate were correlated. Results indicated that cattle that have consumed larkspur will eliminate 99% of MLA and deltaline from serum within 144 hours.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the contribution of 7,8-methylenedioxylycoctonine (MDL)–type alkaloids to the toxic effects of tall larkspur (Delphinium spp) consumption in cattle.

Animals—Sixteen 2-year-old Angus steers.

Procedures—Plant material from 3 populations of tall larkspur that contained different concentration ratios of MDL-type-to-N-(methylsuccinimido) anthranoyllycoctonine (MSAL)–type alkaloids was collected, dried, and finely ground. For each plant population, a dose of ground plant material that would elicit similar clinical signs of toxicosis in cattle after oral administration was determined on the basis of the plants' MSAL-type alkaloid concentration. Cattle were treated via oral gavage with single doses of ground plant material from each of the 3 populations of tall larkspur; each animal underwent 1 to 3 single-dose treatments (≥ 21-day interval between treatments). Heart rate was recorded immediately before (baseline) and 24 hours after each larkspur treatment.

Results—Tall larkspur populations with a lower MDL-type-to-MSAL-type alkaloid concentration ratio required a greater amount of MSAL-type alkaloids to cause the expected clinical signs of toxicosis (including increased heart rate) in cattle.

Conclusions and Clinical Relevance—Results indicated that the typically less toxic MDL-type alkaloids contributed in a significant manner to the toxic effects of tall larkspur in steers. Consequently, both the concentration of MSAL-type alkaloids and the total concentration of MSAL- and MDL-type alkaloids should be determined when assessing the relative toxicity of tall larkspur populations. These results provide valuable information to determine the risk of toxicosis in cattle grazing on tall larkspur–infested rangelands.

Full access
in American Journal of Veterinary Research