Selenium is biologically important because (i) it is essential in animal and possibly plant metabolism, (ii) in many areas diets do not contain sufficient Se to meet animals' needs, and (iii) in other areas it is toxic to animals when it occurrs in high concentrations in soil, water, plants, fly ash, or in aerosols. Animals require 0.05 to 0.1 mg Se/kg in their diets to prevent Se deficiency but suffer Se toxicosis when dietary levels exceed 5 to 15 mg Se/kg. The earth's crustal materials generally contain <0.1 mg Se/kg. Higher concentrations are found in Cretaceous shales. The Se-accumulator plants growing on the seleniferous soils may contain hundreds or even thousands of mg Se/kg. However, the nonaccumulator grasses and forbs seldom accumulate > 50 mg Se/kg and more often contain < 5 mg Se/kg. Soils and plants may discharge volatile forms of Se into the atmosphere. However, plants may also absorb measurable amounts of gaseous Se from the atmosphere. Anthropogenic activities impact the amount of Se entering our nation's lakes, rivers, and the atmosphere. Combustion of coal and incineration of municipal waste exhaust Se into the environment. In addition, crop-fallow and irrigation practices that allow leaching waters to pass through seleniferous strata prior to intersecting with surface flow, augment the Se levels encountered by plant and animal life.

Selenium in certain soils may be taken up by plants in amounts to render them toxic. Seleniferous forage can be found in most of the western states. Intoxication of livestock by seleniferous plants has been classified as acute and chronic. Acute poisoning results from consumption of plants having high levels of Se; chronic Se poisoning has been described in two forms—alkali disease and blind staggers. Alkali disease is said to result from the consumption of seleniferous grains and grasses, and is manifest by loss of hair, lameness, and loss of weight. Blind staggers is said to result from the consumption of Se indicator plants and is manifest by wandering, circling, loss of ability to swallow, and blindness. Some research casts doubt on the above classification of Se poisoning. Research using pigs (Sus scrofa domesticus) indicates that the source of Se does not alter the type of lesion or signs of poisoning observed. There are data available that suggest that blind staggers is not related to Se poisoning.

A. aestivalis collected from Utah, USA, was frozen, freeze dried, ground and administered by gavage to 3 groups of Syrian hamsters each at 0, 250 and 500 mg/kg body weight 4 times a day for 7 days. Serum and tissues were collected after euthanasia. It was shown that clinical, biochemical and histopathological parameters in the control and low (250 mg/kg) groups were unchanged. However, the high dose (500 mg/kg) group developed diarrhoea, anorexia and were reluctant to move. They also had significantly higher serum creatine phosphokinase activities, hyperglycaemia, mild hyponatraemia, hypercreatinaemia and decreased blood urea nitrogen/creatinine ratio. These animals also had extensive haemorrhagic gastroenteritis at necropsy. The stomach, small intestine, colon, caecum and had patchy haemorrhagic and necrotizing enterocolitis. These results indicate that A. aestivalis is also toxic to hamsters as well as livestock.

To test the efficacy of a pyrrolizidine alkaloid (PA) conjugates against riddelline toxicity 90 rats (animal models) were used in this study. The animals were divided into three equal groups of which the two groups were immunized with two riddelline conjugates while the third group served as control. Results showed that all of the rats, including the high dose groups, had minimal response to the riddelline challenge. Though the high dose animals lost more weight than the other groups they were still in good condition with little evidence of liver disease. However high dose animals (25 mg/kg) had a significant increased in ALP, ALT, AST, LDH, bilirubin and bile acid with a decreased in albumin when compared with the low dose group (0, 1, and 5 mg/kg). In conclusion, the rats had poor and variable response to vaccination with few animals developing titres greater than 1:1000. Although there were no significant biochemical differences between the vaccinated and control groups rats with higher titre appear to have less hepatocellular swelling and necrosis.

The aim of this study is to evaluate Switchgrass P. virgatum toxicity in rodents, goats, sheep and horses. Six Syrian hamsters, six gerbils and six guineapigs were randomly divided into two groups and fed with switchgrass pellets or control pellets for 45 days. An additional four groups of three hamsters each were orally dosed with concentrated diosgenin and yamogenin from fenugreek seed to obtain doses of 0, 100, 300, and 900 mg saponins per day. Six horses, six sheep and six goats were also divide into two equal groups and were fed with switchgrass for 90 days. Results after the feeding period showed that most of the animals fed with switchgrass hay loss weight and exhibited poor body condition, none of the horses or sheep nor the rodents fed with switchgrass hay developed serum biochemical changes suggestive of hepatic or renal disease. However, some goats fed with switchgrass hay developed skin lesions consistent with phylloerythrin associated photosensitivity. This findings suggest that switchgrass can be toxic under certain conditions and that young goats are found to be more susceptible to poisoning.

This chapter describes the taxonomy and toxicity of two locoweeds belonging to the genera Astragalus and Oxytropis, each containing several to numerous species of toxic plant species. Those plants with intoxicant properties have led to numerous livestock deaths, amounting to untold amounts of property loss. The first of those genera, Astragalus, is very large, and only a small proportion of the species have been investigated as to their potential for intoxication of livestock. Some 20 species of Astragalus have been noted as poisonous due to the presence of the indolizidine alkaloid swainsonine in their tissues. Species of Astragalus are present in all of the contiguous United States and Alaska, and in all of the Canadian provinces. Oxytropis is much smaller. Species of Oxytropis are confined mainly to western North America, with a few of the taxa extending across the northern portion of the continent to eastern Canada. Four species of Oxytropis are cited as toxic due to the presence of swainsonine.

This discussion of lupine research, past, present and future, is limited to that involving poisoning in livestock and more specifically the problem of the lupine-induced 'crooked calf disease' in the western US.

The clinical, biochemical and histopathological results of various locoweed (Astragalus and Oxytropis spp.) and swainsonine poisoning studies in rats, hamsters, sheep, cattle, horses and mule deer (Odocoileus hemionus) are presented and compared to determine the distribution, severity and nature of locoweed poisoning. Based on the results, all the examined species are susceptible to locoweed poisoning. However, there are species-specific differences in sensitivity to poisoning and the distribution and severity of locoweed-induced lesions. Horses appear to be the most sensitive as they are highly susceptible to the effects of locoweed. Cattle and sheep have a similar susceptibility, while rats, hamsters and mule deer are relatively resistant to locoweed poisoning.

Selenium (Se) plays a critical role in the health and well-being of humans and animals. Deficiency of Se as well as Se toxicosis in animals has been reported from several regions in the United States (Edmonson et ale 1993). Animals residing in Se-deficient areas are often supplemented with Se for optimal growth and production. Due to a relatively low margin of safety, several cases of Se poisoning occur from time to time due to accidental overdosing of injectable Se (sodium selenite with added vitamin E). Natural Se poisoning can also occur in seleniferous areas and areas with high Se contamination, most likely from ingestion of certain plants that can accumulate Se obtained from the soil. Organic Se such as selenomethionine (SeMet) is the major component of Se-accumulating plants (Whanger 2002). In natural settings, chronic selenosis (alkali disease) is more common than acute cases. However, in May 2003, several hundred sheep died acutely after grazing in a Se-rich area in Soda Springs, ID (Fessler et ale 2003). Considerable differences exist between the metabolic pathways of organic and inorganic Se compounds in the body (Ganther 1986). Most of the Se from selenite forms physiologically functional selenoproteins, or is eliminated from the body, whereas a significant portion of the Se from SeMet, in addition to forming functional selenoproteins, is also incorporated into non-functional or structural proteins (Ip 1988). Published literature on acute Se toxicosis predominantly involves sodium selenite (supplementation form of Se). Little is known about such effects of organic See The purpose of this investigation was to reproduce the field toxicosis reported from Soda Springs under experimental conditions using organic selenium (SeMet).

AbstractIn this study, a hypothesis that the pharmacokinetic disposition of anagyrine following repeated challenge, and the response of the fetus, is different in cows that give birth to calves with lupine-induced arthrogryposis than in those that give birth to clinically normal calves was examined. 12 mature cows were obtained from ranches on which calves with lupine-induced arthrogryposis had been born. The cows were challenged with 2 g of dried lupine per kg body weight between 46 and 51 days of the gestation period for the first challenge, and 2.5 g/kg body weight for the 2nd and 3rd challenge between day 60 to 63 and day 68 to 75 respectively. Results: plasma alkaloid concentrations are shown from the two groups of cattle. For the three outcome variables, the differences between the two groups over the three time periods were not statistically significant. Whereas a significant decrease in fetal activity was observed in all cows 4 hours and 12 hours after challenged both at 60 and on the 70th day of pregnancy. There is no evidence in this study to support the differences in metabolism and disposition of anagyrine as a reason for differing birth outcomes in cows under the same lupine-exposure risk. It is probable that this difference between cows reflects differences in amount and timing of lupine consumption.

Ground cutleaf nightshade at 0, 50, 100, 150 and 200 mg in 2 ml of water was fed to 30 Syrian hamsters divided into 5 groups as an animal model for cutleaf nightshade poisoning in horses. The treatments were repeated 4 times a day for 7 days, during which changes in neurologic signs and pupil diameter were monitored. The hamsters were euthanized at the end of the study and blood and tissue samples were collected and analysed. It was shown that none of the treated animals developed cholinergic clinical signs and there were no significant differences in pupil diameter between groups. However, several of the hamsters in the high dose groups developed diarrhoea and small labial ulcerations after several days of treatment. These animals also had sporadic biochemical changes consistent with electrolyte loss and lipid mobilization. At necropsy, hamsters treated with 150 and 200 mg concentrations had segmental dilation of the intestine and stomach. Affected bowels were dilated with gas and mucoid exudates. The mucosa of some animals was red and oedematous, with focally extensive haemorrhagic and necrotizing gastroenteritis which was most severe in the ileum, but also involved the entire small intestine and glandular portion of the stomach. No other significant histologic lesions were found. These findings suggest that cutleaf nightshade toxicity in rodents is due to the direct toxic effects of the glycoalkaloids in the plant. The clinical signs of S. triflorum poisoning in horses are also briefly described.

Locoweed poisoning has been reported in wildlife, but it is unknown whether mule deer (Odocoileius hemionus) are susceptible. In areas that are heavily infested with locoweed, deer and elk (Cervus elaphus nelsoni) have developed a spongiform encephalopathy, chronic wasting disease (CWD). Although these are distinct diseases, no good comparisons are available. The purpose of this study was to induce and describe chronic locoweed poisoning in deer and compare it with the lesions of CWD. Two groups of four mule deer were fed either a complete pelleted ration or a similar ration containing 15% locoweed (Oxytropis sericea). Poisoned deer lost weight and developed a scruffy, dull coat. They developed reluctance to move, and movement produced subtle intention tremors. Poisoned deer had extensive vacuolation of visceral tissues, which was most severe in the exocrine pancreas. Thyroid follicular epithelium, renal tubular epithelium, and macrophages in many tissues were mildly vacuolated. The exposed deer also had mild neuronal swelling and cytoplasmic vacuolation that was most obvious in Purkinje cells. Axonal swelling and dystrophy was found in many white tracts, but it was most severe in the cerebellar peduncles and the gracilis and cuneate fasciculi. These findings indicate that deer are susceptible to locoweed poisoning, but the lesions differ in severity and distribution from those of other species. The histologic changes of locoweed poisoning are distinct from those of CWD in deer; however, the clinical presentation of locoweed poisoning in deer is similar. Histologic and immunohistochemical studies are required for a definitive diagnosis.

The objective of this study is to determine the effects of intermittent locoweed (O. sericea) poisoning on the development of clinical and histological lesions. Results suggest that sheep and possibly cattle may ingest locoweeds for short periods, 5 days or less, if allowed withdrawal periods of 7 to 14 days without developing behavioural or functional lesions.

OBJECTIVE To compare plasma disposition of alkaloids after lupine challenge in cattle that had given birth to calves with lupine-induced arthrogryposis and cattle that had given birth to clinically normal calves and determine whether the difference in outcome was associated with differences in plasma disposition of anagyrine. ANIMALS 6 cows that had given birth to calves with arthrogryposis and 6 cows that had given birth to clinically normal calves after being similarly exposed to lupine during pregnancy. PROCEDURES Dried lupine (2 g/kg) was administered via gavage. Blood samples were collected before and at various time points for 48 hours after lupine administration. Anagyrine, 5,6-dehydrolupanine, and lupanine concentrations in plasma were measured by use of gas chromatography. Plasma alkaloid concentration versus time curves were generated for each alkaloid, and pharmacokinetic parameters were determined for each cow. RESULTS No significant differences in area under the plasma concentration versus time curve, maximum plasma concentration, time to reach maximum plasma concentration, and mean residence time for the 3 alkaloids were found between groups. CONCLUSIONS AND CLINICAL RELEVANCE Because no differences were found in plasma disposition of anagyrine following lupine challenge between cattle that had given birth to calves with arthrogryposis and those that had not, our findings do not support the hypothesis that between-cow differences in plasma disposition of anagyrine account for within-herd differences in risk for lupine-induced arthrogryposis.

Research designed to isolate and identify the bioactive compounds responsible for the toxicity of plants to livestock that graze them has been extremely successful. The knowledge gained has been used to design management techniques to prevent economic losses, predict potential outbreaks of poisoning, and treat affected animals. The availability of these compounds in pure form has now provided scientists with tools to develop animal models for human diseases, study modes of action at the molecular level, and apply such knowledge to the development of potential drug candidates for the treatment of a number of genetic and infectious conditions. These advances are illustrated by specific examples of biomedical applications of the toxins of Veratrum californicum (western false hellebore), Lupinus species (lupines), and Astragalus and Oxytropis species (locoweeds).

Spotted locoweed (Astragalus lentiginosus var. diphysus) is a toxic, perennial plant that may, if sufficient precipitation occurs, dominate the herbaceous vegetation of pinyon-juniper woodlands on the Colorado Plateau. Six cow/calf pairs and four horses grazed a 20-ha pasture with dense patches of locoweed in eastern Arizona during spring 1998. Locoweed density was 0.7 plants/m(2) in the pasture. Locoweed averaged 30.4% NDF and 18.4% CP. Concentrations of the locoweed toxin, swainsonine, fluctuated from 1.25 to 2 mg/g in locoweed. Horses ate more (P < 0.01) bites of locoweed than did cows (15.4 and 5.1% of bites, respectively). Horses generally increased locoweed consumption over time since they ate approximately 5% of bites in the preflower stage compared with 25% of bites in the pod stage. Cattle consumed almost no locoweed (<1% of bites) until the pod stage, when they increased consumption to 15% of bites. Horses were very avid (approximately 65 to 95% of bites) in selecting the small quantities (approximately 40 to 150 kg/ha) of available green grass, and it appeared that their propensity to eat scarce green forage influenced their locoweed consumption as well. Horses ate relatively little dry grass, even when it was abundant, whereas cattle ate large amounts of dry grass until green grasses became more abundant. Calves began eating locoweed on the same day as their dams and ate approximately 20% of their bites as locoweed. Serum concentrations of swainsonine were higher (P < 0.05) in horses than in cattle (433 vs. 170 ng/mL, respectively). Baseline swainsonine was zero in all animals, but swainsonine was rapidly increased to above 800 ng/mL in serum of horses as they ate locoweed. Horses exhibited depression after eating locoweed for about 2 wk; after 5 wk of exposure, horses became anorectic and behaviorally unstable. Although limited in scope, this study indicates that horses should not be exposed to spotted locoweed.

The purpose of this study was to determine whether larkspur toxins conjugated to protein carriers would promote active immunity in mice. Mice were injected with several larkspur toxin-protein conjugates or adjuvant alone to determine whether the resulting immunological response altered animal susceptibility to methyllycaconitine, the major toxic larkspur alkaloid. Although vaccinations increased the calculated lethal dose 50% (LD50) for intravenous methyllycaconitine toxicity, overlapping confidence intervals did not provide evidence of differences between the vaccinated and control groups. In the lycoctonine conjugate (LYC)-vaccinated group, mouse survival was related (P = 0.001) to serum titers for methyllycaconitine doses up to 4.5 mg/kg of body weight. When mice withlow antibody titers were removed from the vaccinated groups in which titer was related to survival, the recalculated LD50 estimates were 20% greater than the LD50 of the control group. However, the 95% confidence intervals of the recalculated LD50 groups overlapped with the control groups. Overall, these results suggest that vaccination altered methyllycaconitine toxicity in mice and that vaccination may be useful in decreasing the effects of larkspur toxins in animals. Additional studies are warranted to continue development of potential larkspur vaccines for livestock.

The objective of this study is to evaluate the effects of animal age on pyrrolizidine alkaloid (PA) toxicity, especially the effects of PAs on neonatal animals. Poisoned 3- and 6-week-old pigs developed clinical signs that were more severe than other age groups. Results suggest that weanling pigs near 3-6 weeks of age are most susceptible to PA poisoning.