Clinical and pathological comparison of Astragalus lentiginosus and Ipomoea carnea poisoning in goats.

The indolizidine alkaloid swainsonine, found in some Astragalus and Oxytropis (i.e., locoweed) species, is a potent cellular glycosidase inhibitor that often poisons livestock. Other toxic genera such as some Ipomoea species also contain swainsonine as well as calystegines which are similar polyhydroxy alkaloids. The toxicity of calystegines is poorly characterized; however, they are also potent glycoside inhibitors capable of intestinal and cellular glycoside dysfunction. The objective of this study was to directly compare A. lentiginosus and I. carnea poisoning in goats to better characterize the role of the calystegines. Three groups of four goats each were treated with ground alfalfa (control), I. carnea or A. lentiginosus to obtain daily doses of 0.0, 1.5, and 1.5 mg swainsonine/kg bw per day, respectively, for 45 days. Animals were observed daily and weekly body weights, serum enzyme activities, and serum swainsonine concentrations were determined. At day 45 all animals were euthanized and necropsied. Goats treated with A. lentiginosus and I. carnea developed clinical disease characterized by mild intention tremors and proprioceptive deficits. Goats treated with A. lentiginosus developed clinical disease sooner and with greater consistency. No differences in body weight, serum swainsonine concentrations and serum enzyme activity were observed between goats treated with A. lentiginosus and I. carnea. Additionally, there were no differences in the microscopic and histochemical studies of the visceral and neurologic lesions observed between goats treated with A. lentiginosus and I. carnea. These findings suggest that I. carnea-induced clinical signs and lesions are due to swainsonine and that calystegines contribute little or nothing to toxicity in goats in the presence of swainsonine.

Detection of swainsonine and calystegines in Convolvulaceae species from the semiarid region of Pernambuco / Detecção de swainsonina e calisteginas em espécies de Convolvulaceae da região semiárida de Pernambuco

Numerous plant species worldwide including some Ipomoea (Convolvulaceae) and Sida (Malvaceae) species in Brazil cause lysosomal storage disease in herbivores and are known to contain swainsonine and calystegines as the main toxic compounds. The aim of this work was to determine swainsonine and calystegines concentrations in species of Convolvulaceae from the semiarid region of Pernambuco. Seven municipalities in the Moxotó region were visited and nine species were collected and screened for the presence of swainsonine and calystegines using an HPLC-APCI-MS method. The presence and concentration of these alkaloids within the same and in different species were very variable. Seven species are newly reported here containing swainsonine and/or calystegines. Ipomoea subincana contained just swainsonine. Ipomoea megapotamica, I. rosea and Jacquemontia corymbulosa contained swainsonine and calystegines. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis and I. incarnata contained just calystegines. The discovery of six Ipomoea species and one Jacquemontia species containing toxic polyhydroxy alkaloids reinforces the importance of this group of poisonous plants to ruminants and horses in the semiarid region of Pernambuco. Epidemiological surveys should be conducted to investigate the occurrence of lysosomal storage disease associated to these new species.(AU)

Numerosas espécies de plantas em todo o mundo, incluindo algumas espécies de Ipomoea (Convolvulaceae) e Sida (Malvaceae) no Brasil, causam doença de armazenamento lisossomal em herbívoros e são conhecidas por conterem swainsonina e calisteginas como princípios tóxicos. O objetivo deste trabalho foi determinar a concentração de swainsonina e calisteginas em espécies de Convolvulaceae da região semiárida de Pernambuco. Sete municípios na região do Sertão do Moxotó foram visitados, onde foram coletadas amostras das folhas de nove espécies de Convolvulaceae para avaliação da presença de swainsonina e calisteginas utilizando-se cromatografia líquida com espectrometria de massa. A presença e concentração destes alcaloides nas folhas de plantas da mesma espécie e dentre as espécies foram muito variáveis. Seis novas espécies de Ipomoea e uma espécie de Jacquemontia contendo swainsonina e/ou calisteginas são relatadas neste estudo. Ipomoea subincana continha apenas swainsonina. Ipomoea megapotamica, I. rosea e Jacquemontia corymbulosa continham swainsonina e calisteginas. Ipomoea sericosepala, I. brasiliana, I. nil, I. bahiensis e I. incarnata continham apenas calisteginas. A descoberta de novas espécies de Ipomoea e Jacquemontia contendo alcaloides polihidroxílicos tóxicos reforçam a importância deste grupo de plantas tóxicas para ruminantes e equinos na região semiárida de Pernambuco. Pesquisas epidemiológicas devem ser realizadas para investigar a ocorrência de doença de depósito lisossomal associada a essas novas espécies.(AU)

Pathogenesis and preventive treatment for animal disease due to locoweed poisoning.

Locoweeds are perennial herbaceous plants included in Astragalus spp. and Oxytropis spp. that contain the toxic indolizidine alkaloid swainsonine. The livestock that consume locoweed feeding can suffer from a type of toxicity called "locoism." There are aliphatic nitro compounds, selenium, selenium compounds and alkaloids in locoweed. The toxic component in locoweeds has been identified as swainsonine, an indolizidine alkaloid. Swainsonine inhibits lysosomal α-mannosidase and mannosidase II, resulting in altered oligosaccharide degradation and incomplete glycoprotein processing. As a result, livestock that consume locoweeds exhibit several symptoms, including dispirited behavior, staggering gait, chromatopsia, trembling, ataxia, and cellular vacuolar degeneration of most tissues by pathological observation. Locoism results in significant annual economic losses. Recently, locoweed populations have increased domestically in China and abroad, resulting in an increase in the incidence of poisoning. Therefore, in this paper, we review the current research on locoweed, including on species variation, pathogenesis, damage and poisoning prevention measures.

Potential degradation of swainsonine by intracellular enzymes of Arthrobacter sp. HW08.

Swainsonine (SW) is a toxin produced by locoweeds and harmful to the livestock industry. Degrading SW by Arthrobacter sp. HW08 was demonstrated as a promising way to deal with SW poisoning. However, it is unknown which part of the subcellular enzymes in Arthrobacter sp. HW08 is responsible for biodegrading SW and whether the metabolites are atoxic. In this study, intracellular and extracellular enzymes of Arthrobacter sp. HW08 were isolated and their enzyme activity was evaluated. The metabolites were fed to mice, and physiological and histological properties of the treated mice were investigated. The results showed that only intracellular enzyme of Arthrobacter sp. HW08 (IEHW08) could degrade SW efficiently. Compared with mice in SW treatment group, mice in SW + IEHW08 treatment group (1) increased their body weights; (2) showed higher number of platelets and lower number of white blood cells; (3) decreased the levels of creatinine, urea nitrogen, alanine transaminase and aspartate aminotransferase in serum; (4) reduced the number of vacuolated cells in cerebellum, liver and kidney. All these data demonstrate that IEHW08 was potentially safe for mice, while keeping the capacity of degrading SW. This study indicates a possible application of IEHW08 as an additive in the livestock industry to protect animals from SW poisoning.

Pathological findings in fetuses of goats and cattle poisoned by Sida carpinifolia (Malvaceae) / Achados patológicos em fetos de caprinos e bovinos intoxicados por Sida carpinifolia (Malvaceae)

In Brazil, the consumption of Sida carpinifolia by livestock has been associated with neurological diseases linked to lysosomal storage disorders. This paper describes the pathological findings in two caprine fetuses from dams that were experimentally poisoned with S. carpinifolia. The goats were orally dosed with 10 and 13g/kg of a paste of green chopped S. carpinifolia for 30 days and were observed for an additional 15 days period after the last dosage with the plant; thereafter they were euthanized and necropsied. The dams showed only slight clinical signs. The study also includes the findings in one bovine fetus from a naturally S. carpinifolia poisoned cow which showed mild incoordination, generalized tremors, staggering, and frequent falls. The cow was euthanized and necropsied. While there were no significant histopathological changes in the goats, in the cow vacuolation of Purkinje neurons of the cerebellum, pancreatic acinar cells, and thyroid follicular cells were observed. The main microscopic changes observed in the caprine and bovine fetuses were vacuolation in the epithelium of renal tubules, thyroid follicular cells, and Purkinje neurons of the cerebellum. Transmission electron microscopy of sections from CNS of the cow and its fetus revealed vacuoles containing fine granular material surrounded by membrane. Lectin-histochemistry of CNS sections from goat fetuses marked lightly to sWGA lectins, WGA, and Con-A.

No Brasil, o consumo de Sida carpinifolia por animais de produção tem sido associada a doenças neurológicas relacionadas com doença de depósito lisossômico. Este trabalho descreve os achados patológicos observados em dois fetos caprinos de mães que foram experimentalmente intoxicadas por S. carpinifolia. As cabras foram intoxicadas experimentalmente com S. carpinifolia nas doses de 10 e 13g/kg durante 30 dias e foram acompanhadas durante 15 dias após o consumo da planta. Após este período foram eutanasiadas e necropsiadas. O estudo também inclui os achados patológicos encontrados em um feto de uma fêmea bovina intoxicada naturalmente pela planta, que mostrou leve incoordenação, tremores generalizados, andar desequilibrado e quedas frequentes. A vaca foi eutanasiada e necropsiada. Embora não houvesse alterações histológicas significativas nas cabras, vacuolização dos neurônios de Purkinje do cerebelo, das células acinares do pâncreas e nas células foliculares da tireoide foram observadas na vaca. As principais alterações histológicas observadas nos fetos caprinos e no feto bovino foram vacuolização no epitélio dos túbulos renais, nas células foliculares da tireoide e nos neurônios de Purkinje do cerebelo. Na microscopia eletrônica de transmissão do sistema nervoso central da vaca e de seu feto revelaram-se vacúolos contendo material finamente granulado e delimitado por membrana. Na técnica de lectina-histoquímica dos fetos caprinos houve marcação leve no SNC para as lectinas sWGA, WGA e para Con-A.

Urinary oligosaccharides: a peripheral marker for Sida carpinifolia exposure or poisoning.

Poisoning by Sida carpinifolia belongs to a group of plant-induced phenotype which resembles lysosomal storage diseases. Saanen goats were fed aerial parts of green S. carpinifolia for up to 3 months. Concentrates complemented the nutritional requirements. Urine and blood samples were collected for oligosaccharide study (by thin layer chromatography-TLC) and hemogram analysis, respectively. Abnormal excretion of oligosaccharides was observed from the 2nd day of S. carpinifolia ingestion until one day after withdrawal of the plant from the diet. There were no changes in hemogram. Clinical signs were typical of poisoning caused by plants of this group and were seen from the 37th day on S. carpinifolia diet until seven days after withdrawal of the plant, when signs gradually became scarce and less evident. Results presented here suggest that detection of urinary oligosaccharides by TLC may be an useful method to assess swainsonine-containing plants exposure or an early diagnostic tool for poisoning by these plants.

Intoxicação por Ipomoea carnea subsp. fistulosa (Convolvulaceae) em caprinos na Ilha do Marajó, Pará / Poisoning by Ipomoea carnea subsp. fistulosa in goats in the Marajó island, Pará

Ipomoea carnea subsp. fistulosa é uma planta que contém swainsonina causando doença de depósito lisossomal em ruminantes, principalmente em caprinos na região Nordeste do Brasil. Para o estudo das plantas tóxicas da Ilha de Marajó, foram visitadas sete propriedades rurais na Ilha de Marajó, seis localizadas no município de Cachoeira do Arari e uma no município de Soure. Em todas as propriedades visitadas as pastagens eram constituídas de campo nativo, tinham pouca disponibilidade de forragem e I. carnea subsp. fistulosa encontrava-se em grande quantidade. Nas três propriedades onde eram criados caprinos foram observados animais com sinais nervosos, incluindo tremores de intenção, aumento da base de sustentação quando em estação, ataxia, hipermetria, nistagmo, paresia espástica ou debilidade, alterações posturais, perda de equilíbrio e quedas. Em duas fazendas a prevalência foi de 32 por cento (23/71) e 100 por cento (32/32) e em outra havia um animal com sinais acentuados e o resto do rebanho, de 19 caprinos, não foi examinado clinicamente. Bovinos, ovinos e bubalinos não foram afetados. Foram eutanasiados e necropsiados seis caprinos que apresentavam sinais clínicos acentuados. Macroscopicamente não foram observadas alterações. Na histologia observou-se vacuolização do pericário de neurônios e do citoplasma de células epiteliais da tireóide, rim, fígado, pâncreas e macrófagos de diversos órgãos. No sistema nervoso central a vacuolização era mais grave nos neurônios de Purkinje do cerebelo e nos neurônios dos núcleos cerebelares e do tronco encefálico. Observaram-se também degeneração walleriana dos axônios e gliose. A alta freqüência da intoxicação nas três fazendas que criavam caprinos sugere que a intoxicação por I. carnea subsp. fistulosa é muito importante para caprinos na Ilha de Marajó, onde há abundante quantidade da planta, que permanece verde durante todo o período seco.

Ipomoea carnea subsp. fistulosa is a swainsonine-containing plant causing a glycoprotein storage diseases in ruminants, mainly in goats in northeastern Brazil. Seven farms were visited on the Marajo Island, state of Pará, northern Brazil, six in the municipality of Cachoeira do Arari and one in the municipality of Soure. In all farms native pastures had shortage of forage and were largely invaded by I. carnea subsp. fistulosa. On the three farms goats presented difficulties in standing, ataxia, hypermetria, wide-based stance, lateral gait, intention tremors, spastic paresis or weakness, abnormal postural reactions, nystagmus, loss of equilibrium and falling to the side or backward. On two farms the prevalence was of 32 percent (23/71) and 100 percent (32/32). On another farm one goat out of 19 had severe clinical signs, but the others of the flock were not examined clinically. Cattle, sheep and buffaloes were not affected. Six goats were euthanized and necropsied. No gross lesions were observed. Upon histological examination the main lesion was the vacuolization of the perikaryon of neurons and cytoplasm of epithelial cells of thyroid, liver, kidney, pancreas and macrophages of different organs. In the central nervous system the vacuolization of the perikaria was more severe in Purkinje cells of the cerebellum and in nuclei of the brain stem, mainly the cerebellar nuclei. Wallerian degeneration of axons and gliosis was also observed. The high frequency of the disease on the three farms suggests that poisoning by I. carnea subsp. fistulosa is very important for goats on Marajó Island where there are large amounts of the plant in the pastures.

Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Turbina cordata in Northeastern Brazil.

A disease of the central nervous system in goats was observed in the municipalities of Juazeiro, Casa Nova and Curaça, state of Bahia, and Petrolina, state of Pernambuco, Northeastern Brazil. The disease was produced experimentally in two goats by the administration of dry Turbina cordata mixed with grain. Clinical signs were observed after the ingestion of 62 and 106 g/kg body weight in 28 and 54 days, respectively. The concentration of swainsonine in the plant varied from less than 0.001% to 0.14% (dry weight). Clinical signs of natural and experimental cases included difficulties in standing, ataxia, hypermetria, wide-based stance, intention tremors, spastic paresis mainly in the hind legs, nystagmus, abnormal postural reactions, head tilting, and falling. Diffuse vacuolation of neurons, epithelial cells of pancreas, thyroids, and renal tubules were observed on the histology. From the electron microscopy of Purkinje cells the vacuoles represented dilated lysosomes. These findings demonstrated that T. cordata causes an acquired glycoprotein lysosomal storage disease. The intoxication occurs at least in an area of 27,000 km2 causing severe losses in goats, and some farmers report the disease also in cattle.

Grazing of spotted locoweed (Astragalus lentiginosus) by cattle and horses in Arizona.

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/m2 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.

Effect of lonophore supplementation on selected serum constituents of sheep consuming locoweed.

The effects of ionophore supplementation on selected serum constituents of sheep consuming locoweed were investigated. Sixteen sheep were allotted by weight to a 2x2 factorial arrangement of treatments: 1) no locoweed, no lasalocid, 2) no locoweed, 0.75 mg lasalocid/kg BW, 3) 0.5 mg swainsonine/kg BW, no lasalocid, 4) 0.5 mg swainsonine/kg BW, 0.75 mg lasalocid/kg BW. Swainsonine was provided by locoweed (Oxytropissericea), and sheep were fed a blue grama based diet at 2.5% BW for a 35 d treatment period. Diets were formulated to be isocaloric and isonitrogenous. Blood samples were collected on d 1, 7,14, 21, 31 and 35 to determine serum swainsonine concentration, alkaline phosphatase, total iron, aspartate aminotransferase, g-glutamyltransferase, and lactate dehydrogenase activity and total cholesterol, and triglyceride concentrations. No lasalocid by locoweed interaction (P > 0.4) was noted for any response variable measured. Average daily gains (P = 0.4) and orts (P = 0.7) were not affected by the treatments. No lasalocid treatment (P = 0.7) or day (P = 0.1) effect of serum swainsonine was observed. A locoweed by day interaction (P < 0.0001) of serum alkaline phosphatase was detected. Alkaline phosphatase levels were elevated (P < 0.01) for locoweed treated sheep at 24 h following initial exposure and remained elevated throughout the trail. Total iron was suppressed (P < 0.08) in locoweed fed sheep. A day effect (P < 0.02) was observed for serum iron. However, no linear, quadratic, or cubic effects of day were noted (P >0.2). A locoweed by day interaction (P < 0.0001) of serum aspartate aminotransferase and g-glutamyltransferase was detected. Aspartate aminotransferase levels were elevated (P < 0.0001) by d 7 for locoweed treated animals and remained elevated throughout the trial. g--Glutamyltransferase levels were suppressed (P < 0.0001) by day 7 for locoweed treated animals and remained suppressed throughout the trial. A locoweed by day interaction (P = 0.06) of serum cholesterol was detected. However, no linear, quadratic, or cubic effects of day were detected (P = 0.2). Lasalocid treatment had no effect on any serum constituent measured. Use of lasalocid in grazing animals should not increase the likelihood of locoweed intoxication.

Identification of swainsonine as a glycoside inhibitor responsible for Sida carpinifolia poisoning.

The indolizidine alkaloid swainsonine has been identified as the toxic constituent of Sida carpinifolia, a native perennial shrub-like plant, reported to produce neurological disorders in goats and ponies in southern Brazil. Swainsonine was detected in dry ground plant material after extraction and analysis by both liquid and gas chromatography mass spectrometry. The swainsonine concentration was 0.006% on a dry weight basis. The clinical and pathological features of this lysosomal storage disease were similar to those observed in Swainsona, Oxytropis, Astragalus, and Ipomoea poisonings with multiple cytoplasm vacuoles in neurons, acinar pancreatic cells, hepatocytes, and renal tubular cells.

Custer, selenium and swainsonine.

The Battle of Little Bighorn was fought over 100 y ago but many controversies remain. Some feel the defeat of Custer could have been avoided if Benteen and Reno had united with Custer. A slow-moving pack train may have hindered the troops of Benteen and Reno from joining up with Custer. One report indicated the horses and mules in the pack train were lame and behaved crazily. It has been previously suggested that the animals had selenium toxicosis. We propose the lameness could have been caused by selenium, but that the behavioral problems may have been caused by the ingestion of plants containing swainsonine.

Neurotoxic mycotoxins: a review of fungal toxins that cause neurological disease in large animals.

Five mycotoxins found in concentrates or roughages have been shown to cause neurologic disease in livestock. Fumonisin B1 is produced by Fusarium moniliforme and causes leukoencephalomalacia in horses. Swainsonine and slaframine are produced by Rhizoctonia leguminicola and cause mannose accumulation and parasympathomimetic effects, respectively. Lolitrems from Acremonium lolii and paspalitrems from Claviceps paspali are tremorgens found in grasses.