HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text 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 toxicosis¹

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

² Corresponding author: Kevin.Welch{at}ars.usda.gov

Although the mechanism of action for larkspur alkaloids has been described, little information is available 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 whether 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 LD₅₀ ranged from 3.3 ± 0.2 to 5.8 ± 0.8 mg/kg of BW. The toxicokinetic profiles of MLA in the susceptible A/J strain and the more resistant 129 strain were compared to determine whether their differences in susceptibility were due to differences in their ability to eliminate MLA. The differences in toxicokinetic variables 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 strain and the susceptible A/J strain. The 129 strain of mice had twice the amount of 7 nAChR subunit expression as the A/J strain, which was in direct proportion to the approximately 2-fold difference in LD₅₀. There was also a significant difference (P < 0.05) in expression of the 3 and 5 nAChR subunits between the 129 and A/J strains, with the 129 strain having a greater expression in each case. These data suggest that the increased susceptibility of the A/J mice could be due to a reduced expression of nAChR subunits. Similar analyses need to be made in cattle to determine whether there is a difference between breeds in susceptibility to larkspur poisoning 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 • lethal dose 50% • methyllycaconitine • mouse strain