Page 891 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

848 SECTION | XIV Poisonous Plants

VetBooks.ir OCH 3 may be quite different due to the fact that tall larkspur is
often ingested repeatedly over 2 4 days.
There are two primary structural features necessary for
toxicity: (1) an N-ethyl bicyclo tertiary alkaloid nitrogen
OCH
H 3 CO 3 atom and (2) a C-18 anthranilic acid ester. Other studies
have also shown that MLA’s aromatic ester function is a
significant haptophore and that the succinimide group
imparts significant toxicity to alkaloids. Two other struc-
N tural features also enhance toxicity: (1) functionality at
OH the anthranilic acid amine nitrogen and (2) functionality
at C-14 (Panter et al., 2002).
Tall larkspur species vary substantially in toxicity,
OH
OCH 3 with a relative ranking (most to least toxic, based on the
MSAL alkaloid content) of D. glaucum (D. brownii in
O Canada), D. barbeyi, D. glaucescens, and D. occidentale.
Generally in tall larkspurs, the concentration of MLA and
O
DAN is highest in immature plant tissue. MLA concentra-
O tions in immature tall larkspurs may exceed 20 mg/g.
Before shattering, tall larkspur pods are relatively high in
toxicity (MLA 1 DAN 5 7 12 mg/g). Toxicity declines
N
rapidly in tall larkspurs once pods begin to shatter.
Measuring plant toxicity early in the growing season may
allow prediction of season-long toxicity and risk (Ralphs
O et al., 2002).
(2) Due to the fact that the MSAL-type alkaloids are much
Methyllycaconitine (MLA)
more toxic than the MDL-type alkaloids, management
recommendations for grazing cattle on larkspur-containing
ranges are based primarily on the concentration of MSAL-
Toxicology
type alkaloids in larkspur (Pfister et al., 2002; Ralphs et al.,
Larkspurs (Delphinium spp.) are a serious toxic problem 2002). However, in many species of tall larkspur, the
for cattle on foothill and mountain rangelands in western MDL-type alkaloids are generally more abundant (Pfister
North America. The toxicity of larkspur plants is due to et al., 1999; Gardner et al., 2002). Research using a mouse
norditerpenoid alkaloids, which occur as one of two model suggested that MDL-type alkaloids enhance the
chemical structural types the 7,8-methylenedioxylycoc- overall acute toxicity of MLA in an additive manner
tonine (MDL) type and the N-(methylsuccinimido) anthra- (Welch et al., 2008). In subsequent studies with cattle, the
noyllycoctonine (MSAL) type. Although the MSAL-type MSAL-type alkaloids such as MLA were the primary fac-
alkaloids are much more toxic (typically .20 3 )(Panter tors responsible for the toxicity of larkspur plants (Welch
et al., 2002), the MDL-type alkaloids are generally more et al., 2010). However, populations of larkspur plants that
abundant in D. barbeyi and D. occidentale populations contained large amounts of MDL-type alkaloids, in addi-
(Gardner et al., 2002). Three MSAL-type alkaloids that tion to high MSAL-type alkaloid content, were found to be
are of primary concern are methyllycaconitine (MLA (2)), more dangerous to cattle than plants with only high
14-deacetylnudicauline (DAN), and nudicauline (NUD). MSAL-type alkaloids. Consequently, for a larkspur plant to
MLA and DAN occur to some extent in all classes of be toxic to livestock, a sufficient quantity of MSAL-type
larkspurs, whereas NUD occurs only in low and plains alkaloids is required. However, MDL-type alkaloids appear
larkspurs. The LD 50 for NUD, MLA, and DAN in mice is to potentiate the overall toxicity of the MSAL-type alka-
2.7, 4.8, and 4.0 mg/ kg intravenously (i.v.), respectively loids and should be considered when predicting potential
(Table 61.3; Panter et al., 2002). The toxic alkaloid con- toxicity of larkspur populations. Therefore, when chemical
centration of the tall larkspur (D. barbeyi) dosed to cattle analyses are performed on larkspur plants to assess their
in a lethality study was not determined. However, data toxic potential, the concentration of both the MSAL-type
from a pen study in which Hereford cattle were dosed via and the total alkaloids should be determined, with more
oral gavage with ground plant material indicate that a weight given to the MSAL-type alkaloids.
lethal dose of D. glaucum is approximately 2.5 g dried MLA and NUD are the dominant toxic alkaloids in
plant material/kg body weight (BW) (unpublished obser- low larkspurs, with concentration ranges of 0.8 4.5 and
vations). The lethal dose in a grazing situation, however, 1 4 mg/g, respectively, for MLA and NUD in low