Page 883 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Poisonous Plants of the United States Chapter | 61 841

VetBooks.ir species of the Astragalus and Oxytropis genera were (Swainsona spp.) were reported a few years before Marsh
reported the details of locoweed poisoning. Ironically, the
responsible, and this research was published in 1909 as a
toxin (swainsonine) was isolated and characterized from
U.S. Department of Agriculture bulletin titled “The
Locoweed Disease of the Plains” by C.D. Marsh. S. canescens and reported in Australia in 1979 (Colegate
There are numerous effects of locoweed on animals, et al., 1979) and subsequently identified and isolated from
but the classic syndrome from which the term “locoism” locoweeds (Astragalus and Oxytropis) in the United
derived is one of neurological dysfunction. The disease is States and reported in 1982 (Molyneux and James, 1982).
a chronic one developing after weeks of ingesting loco- The isolation and characterization of swainsonine from
weeds and beginning with depression, dull-appearing S. canescens resulted from investigations by a multi-
eyes, incoordination progressing to aberrant behavior disciplinary research team in Australia whose members
including aggression, staggering, solitary behavior, and were experienced in various aspects of lysosomal storage
emaciation and ending in death if continued consumption diseases in domestic animals (Dorling et al., 1989). This
is allowed. Other problems associated with locoweed investigation concentrated on the details of the pathogene-
ingestion include reproductive failure, abortion, birth sis of the toxicosis enabling the research team to elucidate
defects, weight loss, and enhanced susceptibility to brisket the mechanism of action, which provided the bioassay
disease at high elevations (Panter et al., 1999b). method for toxin isolation and identification. A review of
Locoweed poisoning affects all animals, but because the historical aspects can be found in Dorling et al. (1989).
of the transient nature of the poisoning, animals removed In essence, the locoism syndrome is a lysosomal storage
from the locoweed early in the toxicosis will recover disease in which α-mannosidase is inhibited, resulting in
most of their function and may be productive animals. In prevention of hydrolysis of mannose-rich oligosaccharides
the final stages of locoism, central nervous system tissue in cells and accumulation of these oligosaccharides result-
shows swelling of axonal hillocks (meganeurites) and ing in cellular dysfunction. Swainsonine has also been
growth of new dendrites and synapses. This altered synap- identified with mixtures of other glycosidase-inhibiting
tic formation in nervous tissue in severely affected ani- polyhydroxy alkaloids in toxic species of Ipomoea, Sida,
mals is permanent and may be the cause of some Solanum, Physalis,and Convolvulus (Asano et al., 1995;
irreversible neurological signs. Because of neurological Haraguchi et al., 2003). Most organ systems are affected,
dys-function and apparent permanence of some lesions in but some are more susceptible, such as glandular and neu-
the nervous system, horses are believed to be rological tissues. Comparative pathology of the glycosidase
unpredictable and therefore unsafe to use for riding, but inhibitors swainsonine, castanospermine, and calystegines
they may remain reproductively sound once they have A3, B2, and C1 in mice was reported (Stegelmeier et al.,
recovered from the poisoning. 2008). Although there were similar vacuolar changes, there
were differences in the organ systems involved and minor
changes in protein glycosylation, and it was determined
Toxin that in mice calystegines and castanospermine are less
toxic than swainsonine.
It has been discovered that swainsonine in Astragalus
OH
OH and Oxytropis species is produced by a fungal endophyte,
H
Undifilum oxytropis (formerly called Embellesia oxytro-
pis). A positive correlation was shown to exist between
swainsonine concentrations found in the plant and con-
OH
centrations of swainsonine produced by the endophytic
N
fungus cultured from the same plant (Pryor et al., 2009;
(1) Cook et al., 2009a). This same correlation was demon-
Swainsonine strated for Oxytropis glabra, an important poisonous plant
The toxin in locoweeds is the indolizidine alkaloid in Inner Mongolia steppe (Ping et al., 2009). Major loco-
swainsonine (1). First isolated from the Australian plant weeds were screened for the presence of endophyte and
Swainsona canescens (Colegate et al., 1979), swainsonine swainsonine content using both culture methods and poly-
and its N-oxide were isolated and identified soon there- merase chain reaction (PCR; Ralphs et al., 2008). PCR
after from the locoweeds (Molyneux and James, 1982). was demonstrated to be the most sensitive method of
Remarkably, in 1909, C.D. Marsh made the connection detecting the endophyte because the endophyte in plants
between the clinical and pathological syndrome of loco- with very low levels of swainsonine (,0.01%) was not
weed poisoning and a similar condition reported in detected by culture methods, only PCR. Oldrup et al.
Australian livestock called “peastruck.” Confirmation (2010) demonstrated that U. oxytropis is transferred by
feeding trials in New South Wales with Darling pea seed and the endopyte resides in the parenchymal layers