Toxicokinetics of norditerpenoid alkaloids from low larkspur (Delphinium andersonii) orally administered to cattle

Benedict T. Green Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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Kevin D. Welch Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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Dale R. Gardner Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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Bryan L. Stegelmeier Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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James A. Pfister Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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Daniel Cook Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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Kip E. Panter Poisonous Plant Research Laboratory, Agricultural Research Service, USDA, 1150 E 1400 N, Logan, UT 84321.

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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.

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.

Contributor Notes

Supported by the USDA Agricultural Research Service.

Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the USDA.

The authors thank Clint Stonecipher, Edward L. Knoppel, Danny Hansen, Scott Larsen, Isabelle McCollum, Kermit Price, Terrie Wierenga, and Rex Probst for technical assistance and Bud Purdy and Nick Purdy for assistance in obtaining low larkspur.

Address correspondence to Dr. Green (Ben.Green@ars.usda.gov).
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