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Surprisingly, toxins can be put to use in human medicine. Just as the botulism toxin (Botox) has been applied to treat wrinkles and to cure migraines, some studies suggest that swainsonine and related plant toxins may have useful application in fighting cancer.
mecanism of action
Members of the genus Astragalus are known by a number of different names. Those most widely used are locoweed and milkvetch. There are over 2000 species in this genus that are known currently, of which many are known to carry various toxins. (Williams, 1984) They can be found in North and South America, Asia, Europe, Northern Africa and Australia. Due to their range and toxicity, livestock poisoning by locoweed is the most widespread toxic plant problem in the western U.S.,(Ralphs, James, Nielsen, Baker, Molyneux, 1988) costing millions of dollars both in livestock loss and in cost of plant control (Williams, 1984) Despite the unpleasant effects of Astragalus poisoning, animals often become habituated to eating, fueling their further intoxication by the plant.(Ralphs, Panter, James, 1990)
Astragali poison in three main ways:
With the indolizidine alkaloid swainsonine
With the nitropropanol bearing glycoside miserotoxin (not in the case of locoweed)
With toxic levels of selenium metabolites (Se)
The selenium indicator plants, of which there are approximately 25, are associated with acute and chronic poisoning.
A. Acute poisoning is rare and is associated with range conditions in which animals are introduced to a new area and simply consume selenium indicator plants at too high a rate of intake. As in other forms of acute selenium poisoning, respiratory failure, pulmonary edema, and shock may cause death within 1 day. Diarrhea and fever may also precede death.
B. Chronic poisoning is of two subtypes:
1. The first is so-called "alkali disease" and occurs after ingestion of seleniferous grasses and selenium accumulators over a long time. The responsible locoweeds may be selenium accumulators and not necessarily selenium indicator plants. Alkali disease is apparently genuine selenium poisoning and is characterized by long hooves, separation of the coronary band, rough hair or loss of the tail and/or mane. The greatest economic loss in alkali disease is diminished reproduction which can often occur without other signs. Although alkali disease affects cattle, sheep and horses, the major reproductive failures occur in the ruminants. Sudden death sometimes occurs in alkali disease of sheep.
2. The second form of chronic poisoning by the selenium accumulating species of locoweeds, blind staggers, is possibly not due to the selenium in these plants. Blind staggers affects cattle and occasionally sheep, but not horses. It has been suggested that blind staggers is really a form of polioencephalomalacia, or is possibly a variant form of "true locoism".
True locoism, which affects all livestock, is the result of ingestion of the indolizidine alkaloid, swainsonine or swainsonine N-oxide. Locoism is characterized by emaciation,habituation, propioception deficits, slow, staggering gait, decreased libido, abortion (can approach 100%), small, weak young, and birth defects, especially bent legs. Impaired function of the liver, pancreas, thyroid, and parathyroid glands contribute to weight loss of locoed animals. Decreased lacrimation and retinal cell vacuolation results in impaired vision. Immunosuppression (decreased T lymphocyte function) has been observed with experimental feeding of locoweed to sheep.
Swainsonine is an alkaloid which inhibits alpha-mannosidase with increase in oligosaccharides inside lysosomes (histolysosomal swelling and vacuolization is prominent). Onset of toxicosis occurs after at least 2 weeks and usually after chronic exposure. Swainsonine gets its name from another legume, the Australian "darling pea", Swainsona spp., which also contains this alkaloid and which causes a syndrome similar to that induced by locoweeds. Horses are especially sensitive to locoism and, once exposed, may be more sensitive to the production of toxic effects and habituation than prior to exposure (this is termed sensitization). Habituation may be manifested by ingestion of all plant parts. This may include eating soil containing the roots of locoweed after other parts of the plants have been grazed. Often significantly poisoned horses may become belligerent and CNS dysfunction may render them useless or dangerous to their owners. The indolizidine alkaloids are passed in milk and calves develop cytoplasmic vacuolation, which may account for unthriftiness.
Groups of cattle grazing locoweed (O. serius) at high altitude and experiencing "true locoism" sometimes also display an increased incidence of right heart failure ("highmountain disease"). The toxic principle causing this latter syndrome has not been defined. (see article in tox)
Understood (in part only):
Methemoglobinemia (Part of II. above).
Nitrites oxidize iron (Fe++) in hemoglobin to form methemoglobin (Fe+++) which cannot carry oxygen.
Some nitro compounds are also capable of complexing with ferrous hemoglobin (Fe++) in blood to produce methemoglobin directly.
Swainsonine (cause of true locoism) (See IV. above).
Inhibits a -mannosidase.
Result is mannosidosis, which is an accumulation of mannose-rich oligosaccharides in vacuoles within neurons, renal tubules, liver, placenta, lymphocytes, etc. (lesion in lymphocytes in peripheral blood is used diagnostically).
Abortion occurs after death of the fetus in association with heart failure.
"3-nitro" related diseases
Acute nonspecific pulmonary congestion, cyanosis.
Chronic hepatic congestion and swelling.
Pulmonary emphysema and pneumonia.
Excessive cerebrospinal fluid.
Ulceration near the cardia of the abomasum in ruminants.
Chronic pulmonary emphysema, edema, fibrosis.
Wallerian degeneration (dying back neuropathy with demyelination) of the spinal cord and peripheral nerves.
Acute selenium poisoning
Pulmonary congestion and edema (see Toxicants that Affect the Respiratory System).
Chronic selenium toxicosis
Rough hair coat, loss of mane or tail.
Erosions of joints of long bones.
Possible cracking and/or irregular hoof growth.
Vacuolization of neurons, renal cortical tubular epithelial cells, hepatocytes, pancreas. Vacuolization of renal tubules appears 4 days after feeding of locoweeds. By day 32 in an experimental study, almost all tissues showed vacuolization. Vacuolization is reversible.
Enlarged thyroid glands.
Retinal damage (vacuolation) and vacuolar degeneration in the lacrimal gland may occur, the latter leading to a "dull eye"
Delayed placentation in ewes, cytoplasmic vacuoles in the placenta.
Abortion, small, weak lambs.
In rams: reduced spermatogenesis; vacuolation of spermatogonia, epithelium of the epididymus and seminal vesicles.
Mild myelin degeneration (with local fluid accumulation) and axonal degeneration with "axonal spheroids" in many areas of the CNS.
Enlargement of lysosomes.
Mitochondrial swelling and degeneration.
Congestive heart failure
Right ventricular enlargement.