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United States Department of Agriculture

Agricultural Research Service

Title: The Toxicity and Kinetics of Larkspur Alkaloid, Methyllycaconitine, in Mice

Authors
item Stegelmeier, Bryan
item Hall, J. - UTAH STATE UNIVERSITY
item Gardner, Dale
item Panter, Kip

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 8, 2003
Publication Date: August 1, 2003
Citation: Stegelmeier, B.L., Hall, J.0., Gardner, D.R., Panter, K.E. 2003. The toxicity and kinetics of larkspur alkaloid, methyllycaconitine, in mice. Journal of Animal Science.

Interpretive Summary: Larkspur poisoning often kills from 5-15% of the cattle on North American mountain rangelands. Of the 40 different poisons found in larkspur, on thought to be the most poisonous is called methyllycaconitine or MLA. Little is known about what happens to MLA in the body or how fast it is eliminated or removed. The purpose of this study was to further characterize the signs MLA toxicity in mice and determine the rate and route of MLA excretion. Eight groups of mice were dosed intravenously with 2.0 mg/kg MLA, euthanized and necropsied at 0, 1, 2, 5, 10, 15, 30 and 60 minutes after injection. Treated animals were reluctant to move, trembled and developed dyspnea, muscular twitches, and convulsions. Within several minutes the clinical signs resolved and behavior slowly returned to normal over about 20 minutes. At necropsy serum, brain, liver, kidney and skeletal muscle were collected and frozen. Blood and tissues were analyzed for MLA using high performance liquid chromatography and electron spray mass spectrometry. Blood MLA elimination followed a normal biphasic redistribution and excretion pattern (R=0.99) with a K of elimination of 0.0376 and half-life of 18.4 minutes. Other tissues had similar clearance rates. These data indicate the MLA is rapidly distributed throughout the body and it is rapidly excreted unchanged in the urine. In mice the clinical effects of poisoning appear to affect the central nervous system causing dyspnea and explosive muscular twitches and convulsions. As livestock commonly eat larkspur at low doses, this suggests that animals exposed to larkspur should rapidly excrete MLA (within several hours) and that the residues in animal tissues are not likely to be a problem if animals are given several days to allow toxin clearance.

Technical Abstract: Larkspur poisoning sporadically kills from 5-15% of the cattle on North American mountain rangelands. Of the 40 different diterpenoid larkspur alkaloids, one that is thought to be responsible for much of larkspur's toxicity has been identified as methyllycaconitine (MLA). Little is known of MLA toxicokinetics or excretion. The purpose of this study was to further characterize the clinical effects of MLA toxicity in mice and determine the toxicokinetics of MLA excretion. Eight groups of mice were dosed intravenously with 2.0 mg/kg MLA, euthanized and necropsied at 0, 1, 2, 5, 10, 15, 30 and 60 minutes after injection. Treated animals were reluctant to move, trembled and developed dyspnea, muscular twitches, and convulsions. Within several minutes the clinical signs abated and behavior slowly returned to normal over about 20 minutes. At necropsy serum, brain, liver, kidney and skeletal muscle were collected and frozen. Blood and tissues were extracted and analyzed for MLA using high performance liquid chromatography and electron spray mass spectrometry. Blood MLA elimination followed a normal biphasic redistribution and excretion pattern (R=0.99) with a K of elimination of 0.0376 and half-life of 18.4 minutes. Other tissues had similar clearance rates. These data indicate the MLA is rapidly distributed and excreted. In mice the clinical effects of poisoning appear to affect the central nervous system causing dyspnea and explosive like muscular twitches and convulsions. As livestock commonly eat larkspur at sub clinical doses, this suggests that animals exposed to larkspur should rapidly excrete MLA (within several hours) and that the residues in animal tissues are not likely to be a problem if animals are given several days to allow toxin clearance.

Last Modified: 12/21/2014
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