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This Article Full Text (PDF) All Versions of this Article: jas.2008-1577v1 87/4/1558    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Welch, K. D. Articles by Stegelmeier, B. L. Search for Related Content PubMed PubMed Citation Articles by Welch, K. D. Articles by Stegelmeier, B. L.

Investigation of the susceptibility of various strains of mice to methyllycaconitine toxicosis

USDA-ARS Poisonous Plant Research Laboratory, Logan, Utah 84341

Kevin.Welch{at}ars.usda.gov

Abstract

Although the mechanism of action for larkspur alkaloids has been described, there is little information on the variation of the physiological response of individual animals to larkspur alkaloids. Anecdotal observations and pilot studies in cattle indicate that there is animal-to-animal variation in response to a debilitating dose of larkspur alkaloids. The objective of this study was to determine if there is variation in susceptibility of different strains of mice to larkspur alkaloid toxicosis and to identify factors responsible for the variation that could then be used as a model for studies in cattle. The acute toxicity of methyllycaconitine (MLA) in 9 different inbred strains of mice was compared. The rank order from most to least susceptible was A/J > B10 > FVB > BALB/c > C57Bl/6 > NZW > C3H > DBA > 129. The calculated LD₅₀s ranged from 3.3 ± 0.2 mg/kg BW to 5.8 ± 0.8 mg/kg BW. The toxicokinetic profiles of MLA in the susceptible A/J and more resistant 129 strains were compared in order to determine if their differences in susceptibility are simply due to differences in their ability to eliminate MLA. The differences in toxicokinetic parameters observed did not explain the differences in susceptibility. The protein expression of various nicotinic acetylcholine receptor (nAChR) subunits was also compared between the more resistant 129 and susceptible A/J strains. The 129 strain of mice had twice the amount of alpha 7 nAChR subunit expression as the A/J strain, which was in direct proportion to the approximate 2-fold difference in LD₅₀. There was also a significant difference (P<0.05) in the expression of the alpha 3 and alpha 5 nAChR subunits between the 129 and A/J strains, with the 129 strain having a higher expression in each case. These data suggest that the increased susceptibility of the A/J mice could be due to a lower expression of nAChR subunits. Similar analyses need to be made in cattle to determine if there is a difference in susceptibility to larkspur poisoning between breeds and to identify the factors that regulate their susceptibility to larkspur poisoning. This information would be useful for livestock producers in their breeding, culling, and grazing management programs to reduce or prevent larkspur poisoning on rangelands.

Key Words: Delphinium • larkspur • LD₅₀ • methyllycaconitine • mouse strains