Page 901 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

856 SECTION | XIV Poisonous Plants

VetBooks.ir following: scoliosis, torticollis, kyphosis, or cleft palate. teratogenic alkaloids are produced in the plants as enan-
tiomeric pairs and exhibit differences in activity using
Elbow joints are often immobile because of malalignment
these specialized cells and when compared using a mouse
of the ulna with the articular surfaces of the distal extrem-
ity of the humerus. The part of the limb distal to the bioassay (Lee et al., 2006, 2008a c). This inhibited fetal
elbow joint is often rotated laterally. In crooked calf dis- activity is responsible for the skeletal contracture malfor-
ease, the osseous changes observed are permanent and mations and cleft palates (Panter et al., 1990a), and a goat
generally become progressively worse as the calf grows model developed in the 1990s using anabasine as the
and its limbs are subjected to greater load-bearing stress. teratogen and ultrasound imaging to evaluate fetotoxicity
Frequently, minor contractions such as “buck knees” often has been utilized for biomedical research to improve
attributed to lupine will resolve on their own and the calf treatments and potential fetal intervention for cleft palate
will appear relatively normal. in children (Panter and Keeler, 1992; Weinzweig et al.,
No breed predilection or genetic susceptibility to the 1999, 2008).
lupine-induced condition has been determined. Likewise,
lactation or age did not influence the propensity for cattle Prevention, Management, and Treatment
to graze lupine (Pfister et al., 2008a). However, body con-
dition was shown to affect the absorption and elimination Keeler et al. (1977) proposed a simple management solu-
half-life of anagyrine in sheep (Lopez-Ortiz et al., 2004). tion to prevent crooked calves: stagger grazing of lupine-
Research on cattle has demonstrated that body condition infested pastures so that the susceptible period of gesta-
impacts absorption, distribution, and elimination of the tion (40 70 days) does not overlap the flower and pod
alkaloids and therefore could impact the risk of toxicity stage of growth when anagyrine is highest. Ralphs et al.
or teratogenic outcome of lupines (Lee et al., 2008d). (2006) refined Keeler’s recommendations to restrict
This difference in toxicokinetics was significant for two access during the susceptible period of gestation, when
teratogenic alkaloids anagyrine and ammodendrine. anagyrine concentration is still high in the flower and pod
The disposition of teratogenic alkaloids in the fetal com- stage, only when cattle are likely to eat lupine, and in
partment is unknown and will require further research. years when it is abundant. Panter (unpublished data) sug-
The sensitive gestational period in the pregnant cow gested that intermittent grazing between lupine pastures
for exposure is 40 70 days with suspicious periods and clean pastures would allow the fetus to regain normal
extending to day 100 (Panter et al., 1997). The condition movement for a few days during the sensitive stage of
has been experimentally induced with dried ground lupine gestation. It has been hypothesized that inhibited fetal
at 1 g/kg BW and with semi-purified preparations of ana- movement over a prolonged period of time is required for
gyrine (the apparent teratogen) at 30 mg anagyrine/kg severe malformations to occur (Panter et al., 1999a).
BW fed daily from 30 to 70 days of gestation. The dose Lupines are easily controlled with 2,4-D-type broad-
range of anagyrine to cause crooked calves is leaf herbicides (Ralphs et al., 1991); however, herbicide
6.5 11.9 mg/kg BW/day for 3 or 4 weeks during gesta- treatment alone rarely provides long-term solutions to poi-
tion days 40 70. Crooked calf disease has also been sonous plant problems. Seed reserves in the soil will rap-
induced by feeding the piperidine alkaloid-containing idly reestablish the stands if grazing management
lupine, L. formosus (Keeler and Panter, 1989). The terato- practices are not implemented.
genic piperidines, ammodendrine, N-acetylhystrine, and Death losses in sheep can be reduced by recognizing
N-methyl ammodendrine, are absorbed quickly after the variability in lupine toxicity with stage of growth and
ingestion and can be detected in blood plasma by 0.5 h, the conditions under which animals graze the plant.
with peak levels maintained for more than 24 h (Gardner Providing a choice of other quality forages usually pre-
and Panter, 1993). The mechanism of action has been vents excess lupine grazing. The dangerous period of
determined to be an alkaloid-induced reduction in fetal plant growth for sheep exists mainly with plants in the
movement by a neuromuscular blocking effect during the pod stage. The hazard increases if sheep are hungry, as is
critical stages of gestation (Panter et al., 1990a). This often the case with crowding, hauling, driving, or over-
inhibition of fetal movement is due to stimulation fol- grazed conditions. The hazard is reduced or eliminated
lowed by desensitization of skeletal muscle-type nAChR when lupine is in post-seed stage.
(Lee et al., 2006). This mechanism is a common factor Treatment for overt poisoning is usually symptomatic,
for multiple alkaloids found in many species of lupines, and recovery is often spontaneous if animals are not
poison hemlock (Conium), and wild tree tobacco (N. glau- stressed further by driving. Once the animal is observed
ca), and research using TE-671 cells that express human showing muscular tremors, it should be allowed to drop
fetal muscle-type nAChR and SH-SY5Y cells that express back and proceed at its own pace. Poisoned animals
human autonomic-type nAChR supports this mechanism should never be forced to continue moving because this
(Green et al., 2010). Interestingly, many of these will exacerbate the clinical effects and can result in death.