Neonatal mortality associated with sodium monofluoracetate in kids fed with colostrum from goats ingesting Amorimia septentrionalis / Mortalidade neonatal associada ao monofluoroacetato de sódio em cabritos alimentados com colostro de cabras ingerindo Amorimia septentrionalis

Sudden deaths after colostrum ingestion in kids and lambs born to mothers grazing in areas with Amorimia septentrionalis have been reported in the Brazilian northeastern semi-arid region, in Paraíba state. This study aimed to determine whether the sodium monofluoracetate (MF) contained in A. septentrionalis is eliminated in milk, causing the death of kids. After confirming gestation on the 25th day after mating, 26 goats were randomly distributed into three groups. In Group 1, eight goats received fresh leaves of A. septentrionalis in daily doses of 1g/kg body weight, administered at three different periods during gestation: from days 91 to 100, 116 to 125, and from day 140 until delivery day. In Group 2, consisting of 10 females, eight goats received 1g/kg body weight of A. septentrionalis dried and milled leaves, fed daily from the 140th day of gestation until delivery. The other two goats of this group did not ingest the plant during gestation and after delivery the colostrum supplied to their kids was replaced by colostrum of goats from that same group that had ingested the plant. Eight goats from Group 3 (control) did not ingest A. septentrionalis. Seven goats from Group 1 showed signs of poisoning from 2nd to 8th days of plant administration, in all periods, and recovered within 7 to 12 days. Another goat presented severe clinical signs and was submitted to euthanasia in extremis. Two goats aborted. Four kids, from two goats, received colostrum and, after 15 minutes, presented depression, breathing wheezing, lateral recumbence, bleating, and death. Two goats gave birth at night; the two kids were found dead and, at necropsy, it was verified that they were born alive. The last goat in this group gave birth to two kids which showed no signs of poisoning after colostrum ingestion. In Group 2, the eight goats that ingested dry leaves of the plant presented tachycardia and engorgement of the jugular veins; six aborted, and the kids of the other two goats died immediately after delivery without ingesting colostrum. The three kids of the two goats that did not ingest the plant during gestation did not show signs of poisoning after ingesting colostrum from the goats that had ingested the plant. In Group 3, all females kidded normally and the kids showed no signs of poisoning. Ten leaf samples of A. septentrionalis contained 0.00074% ±0.00018 MF. These results demonstrate that the MF of A. septentrionalis is eliminated in colostrum and may cause the death of kids. As in previous reports, the plant also caused abortion.(AU)

Mortes súbitas, após a ingestão do colostro, em cabritos e cordeiros nascidos de mães que pastejam em áreas com Amorimia septentrionalis são relatadas no semiárido da Paraíba. O objetivo deste trabalho foi determinar se o monofluoracetato de sódio (MF) contido em Amorimia septentrionalis é eliminado pelo leite, causando a morte dos cabritos. Após a confirmação da gestação no 25º dia após a cobertura, 26 cabras foram aleatoriamente distribuídas em três grupos. No Grupo 1, oito cabras receberam folhas frescas de A. septentrionalis em doses diárias de 1g/kg de peso vivo, administradas em três períodos diferentes durante a gestação: entre os dias 91 a 100, 116 a 125 e do 140º dia até o parto. No Grupo 2, composto por 10 fêmeas, oito cabras receberam 1g/kg de peso vivo de folhas secas e trituradas de A. septentrionalis, fornecida diariamente do 140º dia de gestação até o parto. As outras duas cabras desse grupo não ingeriram a planta durante a gestação e, ao parirem, o colostro fornecido aos seus cabritos foi substituído pelo colostro de cabras, desse mesmo grupo, que ingeriram a planta. Oito cabras do Grupo 3 (controle) não ingeriram A. septentrionalis. Sete cabras do Grupo 1 apresentaram sinais de intoxicação entre o 2º e 8º dia de administração da planta, em todos os períodos, e se recuperavam em 7 a 12 dias. Outra apresentou sinais clínicos graves e foi eutanasiada in extremis. Duas cabras abortaram. Quatro cabritos, oriundos de duas cabras, receberam colostro e, após 15 minutos, apresentaram depressão, respiração ofegante, decúbito lateral, berros e morte. Dois cabritos, nascidos de duas cabras que pariram durante a noite, foram encontrados mortos e os achados de necropsia permitem afirmar que nasceram vivos. A outra cabra desse grupo pariu dois cabritos que, mesmo mamando o colostro, não apresentaram sinais de intoxicação. No Grupo 2, as oito cabras que ingeriram a planta seca apresentaram taquicardia e ingurgitamento das veias jugulares; seis abortaram e os cabritos das outras duas morreram imediatamente após o parto, sem ingerir colostro. Os três filhotes das duas cabras que não ingeriram a planta durante a gestação não apresentaram sinais de intoxicação após ter ingerido colostro das cabras que tinham ingerido a planta. No Grupo 3, todas as fêmeas pariram normalmente e os filhotes não apresentaram sinais de intoxicação. Dez amostras de folhas de A. septentrionalis continham 0,00074% ± 0,00018 de MF. Estes resultados demonstram que o MF de A. septentrionalis, além de causar abortos, é eliminado pelo colostro podendo causar a morte dos cabritos.(AU)

Toxicity of the different vegetative stages of Amorimia pubiflora to sheep.

Toxic plants containing monofluoroacetate (MFA) cause sudden death in livestock in Australia, South Africa and Brazil, causing economic losses to producers. The objective of this study was to determine the amount of MFA present in young leaves, mature leaves, senescent leaves, and seeds of Amorimia pubiflora harvested at different times of the year and to determine their toxic effect on sheep. Samples of Amorimia pubiflora were collected during April, August and December of 2015 and March of 2016, separated according to the vegetative stage (young leaves, seeds, mature leaves, and senescent leaves), dried in an oven, and administered in daily doses of 5 g/kg/body weight (bw) of fresh leaves to sheep through ruminal cannulae. The experiment was divided into four stages according to the time of collection of the plant so that each sheep received a different vegetative stage of the plant (young leaves, mature leaves, and senescent leaves). Only in the second stage of the experiment was it possible to collect A. pubiflora seeds, which were administered using the same method used for the administration of the leaves. The sheep were dosed with the plant until they showed clinical signs of toxicosis or until the plant was no longer available. Aliquots of leaves and seeds of A. pubiflora were analyzed for MFA concentration. The seeds and young leaves had higher concentrations of MFA than did the mature (harvested in August and December) and senescent (harvested in December) leaves. However, all vegetative stages of the plant were toxic and caused fatal poisoning. The results of our study showed that A. pubiflora is toxic to sheep even when MFA concentrations are low, demonstrating that the presence of this substance is a risk factor for the occurrence of poisoning. Knowing the toxic principle and its variations allow us to determine the conditions for the occurrence of plant toxicosis as well as possible treatment, control, and prophylaxis methods, contributing significantly to the reduction of economic losses on farms due to plant poisoning.

Embryonic death and abortion in goats caused by ingestion of Amorimia septentrionalis / Mortalidade embrionária e abortos em cabras causados pela ingestão de Amorimia septentrionalis

Amorimia spp. are sodium monofluoroacetate (MFA) containing plants causing sudden death in ruminants. In a previous study, Amorimia rigida caused abortion in one of the five pregnant sheep that received the plant suggesting that it may cause reproductive losses. This work aimed to study the embryotoxic and fetotoxic effects of Amorimia septentrionalis in goats in the Brazilian northeastern semi-arid region. The effects of A. septentrionalis on pregnancy were studied in 16 goats, divided into four groups according to their gestational period. In Groups 1, 2 and 3 the administration of A. septentrionalis at the daily dose of 5g of leaves per kg body weight was started on the 18th, 36th and 93th days of gestation, respectively. Goats from Group 4 did not ingest the plant. When the goats presented severe signs of poisoning the administration of the plant was suspended. Groups 1, 2 and 3 ingested the plant for 7.25±2.87, 9.25±2.21 and 12.50±0.57 days, respectively. All the goats recovered 7-12 days after the end of the administration of the plant. In Group 1, all the goats had embryonic death 6.25±3.59 days after the end of the ingestion of the plant. In Group 2, three goats aborted at 53, 54 and 78 days of gestation. Two goats from Group 3 gave birth normally and the other two aborted at 114 and 111 days of gestation. It is concluded that Amorimia septentrionalis is a sodium monofluoracetate-containing plant that causes embryonic deaths and abortions in goats that ingest non-lethal doses of the plant.(AU)

Amorimia spp. são plantas que contém monofluoroacetato de sódio (MFA), responsáveis por causar morte súbita em ruminantes. Em estudo prévio, Amorimia rigida causou aborto em uma de cinco ovelhas prenhas que receberam a planta, sugerindo que pode causar perdas reprodutivas. Este trabalho teve como objetivo estudar os efeitos embriotóxicos e fetotóxicos de Amorimia septentrionalis em caprinos na região semi-árida nordestina brasileira. Os efeitos de A. septentrionalis na prenhez foram estudados em 16 cabras, divididos em quatro grupos de acordo com seu período gestacional. Nos grupos 1, 2 e 3 a administração de A. septentrionalis foi diária, na dose de 5g de folhas por kg de peso corporal, iniciada nos dias 18, 36 e 93 da gestação, respectivamente. As cabras do grupo 4 não ingeriram a planta. Quando as cabras apresentavam sinais severos de intoxicação suspendia-se a administração da planta. Os grupos 1, 2 e 3 ingeriram a planta por 7,25±2,87, 9,25±2,21 e 12,50±0,57 dias, respectivamente. Todas as cabras se recuperaram 7-12 dias após o final da administração da planta. No grupo 1, todas as cabras apresentaram quadros de mortalidade embrionária 6,25±3,59 dias após o término da ingestão da planta. No grupo 2, três cabras abortaram aos 53, 54 e 78 dias de gestação. Duas cabras do Grupo 3 deram à luz normalmente e as outras duas abortaram aos 114 e 111 dias de gestação. Conclui-se que Amorimia septentrionalis é uma planta que contém monofluoroacetato de sódio e pode ocasionar mortes embrionárias e abortos em cabras que ingerem doses não letais da planta.(AU)

Intoxicação experimental por Niedenzuella stannea (Malpighiaceae) em ovinos / Experimental poisoning by Niedenzuella stannea (Malpighiaceae) in sheep

Niedenzuella stannea é uma planta que contém monofluoracetato de sódio e é incriminada como causa de morte súbita em bovinos na Região Sul do Estado de Mato Grosso. Este estudo descreve a toxidez e achados clínicos e patológicos da intoxicação experimental por N. stannea em ovinos. Foram utilizados no experimento, frutos, folhas maduras e folhas jovens de N. stannea coletadas em propriedades as margens de afluentes das bacias hidrográficas do Rio Araguaia onde havia histórico de morte súbita em bovinos. Folhas maduras em doses entre 10 e 40g/kg e frutos na dose de 10 g/kg não causaram alterações clínicas. Alterações clínicas foram observadas em ovinos que receberam a partir de 5g/kg de folhas jovens em dose única e a morte ocorreu nos que receberam a partir de 30g/kg. A toxicidade na dose de 30g/kg se manteve após a secagem da planta. Os principais sinais clínicos foram anorexia, apatia, dispneia, arritmia e taquicardia em evolução clínica que variou de 16 às 20h. Notou-se em uma fase terminal hiperaguda, com evolução de 13 a 20 min., relutância ao movimento, micção frequente, jugular ingurgitada, pulso venoso evidente, tremor muscular, decúbito esternal e decúbito lateral e morte. Na necropsia os principais achados foram ingurgitamento de grandes veias, das aurículas do coração e edema pulmonar. Microscopicamente a principal alteração ocorreu no rim e caracterizou-se por degeneração hidrópico-vacuolar no citoplasma de epitélio de túbulos contorcidos distais. Conclui-se que N. stannea na fase de brotação é tóxica para ovinos e que a intoxicação por esta planta deve ser incluída no diagnóstico diferencial das doenças com curso clínico hiperagudo ou morte súbita em ovinos em regiões onde a planta existe.(AU)

Niedenzuella stannea a sodium monofluoroacetate-containing plant cause sudden death in cattle in southern Mato Grosso State. This investigation describes the toxicity and clinical and pathological findings of experimental poisoning by N. stannea in sheep. Fruits, mature leaves and young leaves of the plant collected in properties near the margins of the Araguaia river basins with history of sudden death in cattle were used in the experiment. No clinical signs were observed in sheep ingesting doses between 10 and 40g/kg of mature leaves and 10g/kg of fruits. The animals had shown clinical signs when received young leaves of the plant orally in a single dose of 5, 10, 20g/kg, and death occurred in sheep receiving 30g/kg. The plant at the dose of 30g/kg of fresh leaves maintained its toxicity after being dried. The main clinical signs observed were anorexia, lethargy, dyspnea, tachycardia, and arrhythmia with a clinical course ranging 16-20 hours after the onset of clinical signs. In an hyperacute terminal phase the animals showed reluctance to move, frequent urination, engorged jugular, evident venous pulse, muscle tremor, sternal recumbence, lateral decubitus, and death. At necropsy engorgement of the atrium and large veins of the heart, and pulmonary edema were observed. Microscopically, the kidney had hydropic-vacuolar degeneration in the cytoplasm of the epithelial cells of the distal convoluted tubules. It is concluded that young leaves of N. stannea can cause intoxication in sheep and should be considered in the differential diagnosis of acute diseases or sudden death in sheep in regions where the plant exist.(AU)

Sudden death associated with Niedenzuella stannea (Malpighiaceae) in cattle in the State of Mato Grosso, Brazil: importance and epidemiological aspects / Morte súbita associada a Niedenzuella stannea (Malpighiaceae) em bovinos no Estado de Mato Grosso: importância e investigação epidemiológica

The aim of this study was to investigate the importance of an acute disease that was characterized by sudden death associated with exercise that affected cattle in the region of the Araguaia River, especially in the municipality of Torixoréu, southeastern Mato Grosso, Brazil. Between August and September 2013, eighty farms in the municipality were visited and the pastures of these farms were inspected. Epidemiological questionnaires were completed from 65 farms. A plant identified as Niedenzuella stannea (N. stannea) of the Malpighiaceae family was attributed to the cause of sudden death in cattle, what causes major economic losses. Sudden death reports have occurred since 1970, when livestock was introduced into the region, and sudden death reports still occur. Outbreaks were reported to occur from May to October, but mainly during the dry season between June and August. N. stannea was identified at 41 farms and was always found in near to rivers. The most effective plant control methods included plowing the pastures and fields followed by manual application of Tordon® (Picloram and 2.4D). The administration of 5g/kg of young leaves which were collected from a farm with a sudden death history in cattle also caused sudden death in a sheep. Thus, it is concluded that the sudden death of cattle in the region of the Araguaia River is caused by the consumption of N. stannea.(AU)

O objetivo deste trabalho é relatar a investigação sobre uma enfermidade de caráter agudo, caracterizada por morte súbita associada ao exercício, que acomete bovinos na região de bacias hidrográficas do Rio Araguaia, especialmente no município de Torixoréu, sudeste do estado de Mato Grosso, Brasil. Entre agosto e setembro de 2013, foram visitadas e inspecionadas as pastagens em 80 propriedades rurais do município, e em 65 aplicado um questionário epidemiológico. Uma planta identificada como Niedenzuella stannea (Malpighiaceae), é incriminada como causadora de morte súbita em bovinos gerando grandes prejuízos econômicos. Relatos de morte súbita datam desde 1970, quando a pecuária começou a ser inserida na região, e ocorrem até os dias atuais. Surtos ocorreram em diferentes meses do ano, variando de maio a outubro, sendo a maior parte concentrada durante o período de seca, especialmente nos meses de junho a agosto. N. stannea foi identificada em 41 propriedades, sendo presente próxima aos leitos de rios. Os métodos de controle da planta relatados como mais eficazes foram o arar da pastagem e roça manual seguida da aplicação de Tordon® (Picloram e 2,4D). A administração para um ovino, de 5g/kg de folhas em brotação de N. stannea, coletadas em uma propriedade com histórico de morte súbita em bovinos, reproduziu o quadro de morte súbita. Conclui-se que as mortes súbitas em bovinos em áreas da bacia hidrográfica do rio Araguaia se devem ao consumo de N. stannea.(AU)

[Acute toxicity study of Aspidopterys obcordata aqueous extract in Sprague-Dawley rats].

OBJECTIVE: To examine the acute toxicity of an aqueous extract of Aspidopterys obcordata (A. obcordata) in Sprague Dawley rats. METHODS: The rats were orally administered a dose of 5000 mg/kg body weight and observed continuously for 6 h and then daily for 14 days. Control rats were administered distilled water. The effect of the extract on general behavior, body weight, and food and water intake were measured. After 14 days, the rats were sacrificed and their organs (liver, heart, spleen, lungs, kidney, adrenal glands, ovaries, and testes) were removed for macroscopic examination. The body and organ weights in addition to hematology (e.g., hemoglobin and white blood cell counts) and clinical blood biochemistry (e.g., albumin and bilirubin) were also examined. RESULTS: There were no deaths recorded, and the rats treated with A. obcordata showed no signs of toxicity. All measured parameters in rats treated with A. obcordata were unaffected when compared with those in control rats. The acute toxicity (LD50) was estimated to be > 5000 mg/kg body weight. CONCLUSION: Our results demonstrate the safety of an acute oral administration of an aqueous extract of A. obcordata in rats and indicate that future subacute and long-term toxicity testing of A. obcordata is warranted.

Protection against Amorimia septentrionalis poisoning in goats by the continuous administration of sodium monofluoroacetate-degrading bacteria.

The intraruminal inoculation of sodium monofluoroacetate (MFA)-degrading bacteria has been proposed as a method to prevent poisoning by MFA-containing plants. In previous experiments, MFA-degrading bacteria were inoculated intraruminally before or concurrent with plant challenge, with both strategies conferring partial protection to poisoning. To evaluate the protection to Amorimia septentrionalis poisoning provided by the continuous inoculation of MFA-degrading bacteria isolated from plants and soils, 18 goats were divided into three experimental groups of six animals each: Group 1 goats received daily doses of a mixture of Paenibacillus sp. and Cupriavidus sp., and Group 2 goats received a mixture of Ralstonia sp. and Burkholderia sp., for 40 days, while Group 3 goats were not inoculated. Ten days after initiation of bacterial inoculation in Groups 1 and 2, all goats were challenged daily with 5 g/kg body weight of green leaves from A. septentrionalis. Four goats from Group 1 consumed the leaves throughout the 30-day consumption period and showed clinical signs such as transient tachycardia and engorgement of the jugular. The two remaining animals from Group 1 showed obvious signs of intoxication, and plant administration was suspended on days 17 and 19. The goats in Group 2 consumed the leaves throughout the 30-day study without showing signs of poisoning. The goats from Group 3 (control) manifested severe clinical signs of poisoning between the 3rd and 10th days following the start of the A. septentrionalis challenge. Under the conditions of this experiment continuous intraruminal administration of Ralstonia sp. and Burkholderia sp. provided complete protection to poisoning by A. septentrionalis in goats, while continuous intraruminal administration of Paenibacillus sp. and Cupriavidus sp. provided partial protection.

Administração repetida de doses não tóxicas de monofluoroacetato de sódio não protege contra a intoxicação por este composto em ovinos / Repeated administration of non-toxic doses of sodium monofluoroacetate does not protect against poisoning by this compound in sheep

Com o objetivo de avaliar se repetidas doses não tóxicas de monofluoroacetato de sódio (MFA) induzem resistência à intoxicação por essa substância, 18 ovinos foram distribuídos aleatoriamente em dois grupos experimentais de nove animais cada. Os ovinos do Grupo 1 ingeriram doses crescentes não letais de MFA por seis períodos: 0,05mg/kg por 5 dias; 0,08mg/kg por 4 dias; 0,08mg/kg por 4 dias; 0,1mg/kg por 3 dias; 0,1mg/kg por 3 dias e 0,25mg/kg por 3 dias. Entre o primeiro e o segundo período de administração e entre o segundo e o terceiro período os animais não receberam o MFA por 10 dias consecutivos; entre o terceiro e o quarto período e dentre os demais períodos de administração, os ovinos permaneceram 15 dias sem ingerir o MFA. Quinze dias após o último período de administração os ovinos foram desafiados com a dose única de 1mg/kg de MFA. O Grupo 2 não foi adaptado a ingestão de MFA, estes ovinos receberam dose única de 1mg/kg de MFA no mesmo período em que o G1 foi desafiado. No desafio sete ovinos do Grupo 1 apresentaram sinais clínicos da intoxicação e um ovino se recuperou. No Grupo 2 todos os animais manifestaram quadro clínico da intoxicação por MFA, no entanto, dois ovinos se recuperaram. Os coeficientes de mortalidade foram de 66,6 por cento para o Grupo 1 e de 77,7 por cento para o Grupo 2. Os resultados deste trabalho sugerem que a administração repetida de doses não tóxicas de MFA não protege contra a intoxicação aguda por este composto, portanto, outras alternativas para a profilaxia da intoxicação por plantas que contêm MFA deverão ser pesquisadas, principalmente a utilização intraruminal de bactérias que hidrolisam MFA.

With the objective to assess whether repeated non-toxic doses of sodium monofluoroacetate (MFA) induce resistance to poisoning by this compound, 18 sheep were randomly divided into two experimental groups of nine animals each. Sheep from Group 1 ingested non-lethal increasing doses of MFA for six periods: 0.05mg/kg for 5 days; 0.08mg/kg for 4 days; 0.08mg/kg for 4 days; 0.1mg/kg for 3 days; 0.1mg/kg for 3 days and 0.25mg/kg for 3 days. Between the first and second period of administration and between the second and third period the animals did not receive MFA for 10 consecutive days, between the third and fourth period and during the remaining periods of administration the sheep were left 15 days without ingesting MFA. Group 2 was not adapted to the ingestion of MFA and received a single dose of 1mg/kg of MFA at the same time that Group 1 was challenged. After challenge, seven sheep of Group 1 showed clinical signs of poisoning and one sheep recovered. In Group 2, all animals showed clinical signs of poisoning by MFA, however two sheep recovered. The mortality rate was 66.6 percent in Group 1 and 77.7 percent for Group 2. These results suggest that repeated administration of non-toxic doses of MFA does not protect against acute poisoning by this compound; therefore other alternatives of prophylaxis for poisoning by plants containing MFA should be searched, mainly the use of intraruminal bacteria that hydrolyze MFA.

Induction and transfer of resistance to poisoning by Amorimia (Mascagnia) septentrionalis in goats.

Amorimia septentrionalis contains sodium monofluoroactetate (MFA) and can cause acute heart failure in ruminants when ingested in toxic doses. In this study, we demonstrate that resistance to poisoning by A. septentrionalis can be improved in goats by the repeated administration of non-toxic doses of A. septentrionalis. We also show that increased resistance to poisoning by A. septentrionalis can also be achieved by the transfaunation of ruminal content from goats previously conditioned to be resistant to naïve goats. These methods of improving resistance require further study, but appear to provide potential management solutions to mitigate toxicity problems from A. septentrionalis, and perhaps other plant species containing MFA.

Importância da intoxicação por Amorimia pubiflora (Malpighiaceae) em bovinos em Mato Grosso: reprodução experimental da intoxicação em ovinos e bovinos / The importance of poisoning by Amorimia pubiflora (Malpighiaceae) in cattle in Mato Grosso: experimental reproduction of the poisoning in sheep and cattle

No município de Colniza, Mato Grosso, a principal limitação para expansão pecuária é a ocorrência de "morte súbita" em bovinos, com registros de mortalidade próxima a 50% dos animais. Em visitas realizadas em áreas de ocorrência do problema, nos anos de 2004, 2011 e 2012, constatou-se que havia coincidência entre a ocorrência de "mortes súbitas" no rebanho e a presença de Amorimia pubiflora nas pastagens. As mortes ocorrem durante todo ano, porém acentuam-se no início do período das chuvas, quando há maior quantidade de brotação nas áreas de pastoreio. A intoxicação foi reproduzida em ovinos e bovinos através da administração de folhas jovens coletadas em dois períodos do ano, e, em ovinos, através de folhas maduras e dos frutos. Nos ovinos que morreram, as primeiras manifestações clínicas foram observadas entre 34min e 17h34min após a administração da planta e a evolução clínica foi de 3min a 15h20min, com uma fase final superaguda de 3 a 21min. As principais alterações clínicas encontradas foram taquicardia, evidenciação da jugular, tremores musculares, apatia e relutância à movimentação. Todos os sinais acentuavam-se após a movimentação. A fase final superaguda foi caracterizada por relutância para caminhar, cifose, tremores e contrações musculares generalizadas, principalmente de membros, cabeça e pescoço. Notou-se também taquipneia com respiração abdominal, decúbito esternal e rapidamente lateral ou quedas em decúbito lateral, opistótono, nistagmo e cianose de mucosa oral, seguidos de morte. As folhas jovens, independentemente do período da coleta, foram mais tóxicas; causaram a morte de ovinos a partir de 2g/kg e de um bovino que ingeriu 3g/kg. Já as folhas maduras revelaram-se tóxicas e causaram morte na dose de 20g/kg e os frutos ocasionaram a morte de um ovino que ingeriu 5g/kg. Concluímos que monofluoracetato de sódio (MFA), encontrado na concentração de 0,015% nas folhas em brotação de A. pubiflora, é o princípio tóxico responsável pela "morte súbita" causada por Amorimia pubiflora. Esse estudo mostra a importância de A. pubiflora para a região Centro-Oeste do Brasil, principalmente para a pecuária bovina do município de Colniza, MT. Essa planta é tóxica, também, para ovinos e o quadro clínico é similar ao descrito para bovinos.

In the county of Colniza, Mato Grosso, the main limitation for livestock production is the occurrence of "sudden death" in cattle, which affects in some farms up to 50% of the herd. In visits to some of the farms where the problem occurred, in 2004, 2011 and 2012, the presence of Amorimia pubiflora on the pastures was associated with the occurrence of "sudden deaths" in cattle. The deaths occurred throughout the year, however more frequently at beginning of the rainy season, when A. pubiflora sprouts in the grazing areas. The poisoning was experimentally reproduced in sheep and cattle by the administration of young leaves of the plant collected during two seasons, and in sheep by the administration of mature leaves and fruits. In the sheep that died, the first clinical signs were observed between 34min and 17h34min after the administration of the plant, and the clinical course varied from 3min to 15h20min, with a final peracute phase of 3 to 21 minutes. The main clinical signs were tachycardia, engorgement of the jugular veins, muscle trembling, apathy and reluctance to move, which were more evident when the animals were moved. The peracute final phase was characterized by generalized tremors and muscle contractions mainly of limbs, head and neck, respiratory distress and abdominal respiration, sternal and quick lateral recumbence or falling to the ground with peddling movements, opisthotonus, nystagmus, nystagmus and cyanosis of the oral mucosa, followed by death. The young leaves of A. pubiflora, independent of the collection period, were more toxic and caused death of sheep and cattle after ingestion of 2g/kg and 3g/kg respectively. Mature leaves caused death at the dose of 20g/kg, and the fruits at 5g/kg. The young leaves contained 0.015% of sodium monofluoracetate which is responsible for clinical signs of the "sudden death". These findings show the importance of Amorimia pubiflora for cattle raising in Midwestern Brazil. The plant is toxic also for sheep causing a clinical picture similar to that reported in cattle poisoned by monofluoracetate-containing plants.

Decreased expression of cardiac troponin C is associated with cardiac lesions in Amorimia exotropica poisoned cattle / Expressão diminuída de troponina cardíaca C associada com lesões cardíacas em bovinos intoxicados por Amorimia exotropica

The plants which cause sudden death of cattle in Brazil occupy a leading position for losses in the cattle industry. Amorimia exotropica is one of the plants pertaining to this group. Diagnostic findings in these cases may be inconclusive; further knowledge is necessary. This paper identifies cardiac lesions through anti-cardiac troponin C (cTnC) immunehistochemistry performed in tissues from cattle poisoned after consumption of A.exotropica in southern Brazil. Heart fragments from nine A. exotropica-poisoned cattle were studied immunohistochemically using anti-human cTnC as the primary antibody. In the hearts from all of the poisoned cattle, there was a sharp decrease in the cTnC expression level in the cytoplasm of groups of cardiomyocytes. A significant decrease in anti-cTnC immunoreactivity occurred particularly in degenerated or necrotic cardiomyocytes. Occasional groups of cells showed complete loss of immunolabeling. In the remaining intact cardiomyocytes from poisoned cattle and in cardiomyocytes from six cattle that died from other causes there was intense cytoplasmic staining.

No Brasil, plantas cujo consumo determina morte súbita de bovinos estão entre as principais causas de perdas na pecuária. Esse trabalho identifica lesões cardíacas através de imuno-histoquímica antitroponina cardíaca C (TncC), desenvolvida em tecidos de bovinos intoxicados após consumo de Amorimia exotropica, no sul do Brasil. Fragmentos cardíacos de nove bovinos intoxicados, naturalmente, por Amorimia exotropica foram examinados por imuno-histoquímica anti-TncC, como anticorpo primário. Nos corações de todos os bovinos intoxicados pela planta, havia pronunciada diminuição dos níveis de expressão de TncC no citoplasma de grupos de cardiomiócitos. Diminuição significativa na imunorreatividade anti-TncC ocorreu, particularmente, em cardiomiócitos degenerados ou necróticos. Grupos ocasionais de células mostraram completa perda de imunomarcação. Em cardiomiócitos remanescentes e intactos de bovinos intoxicados e em cardiomiócitos de seis bovinos que morreram por outras causas, observou-se intensa coloração citoplasmática.

Anti-inflammatory, anti-hyperalgesic, antiplatelet and antiulcer activities of Byrsonima japurensis A. Juss. (Malpighiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions or infusions of the stem bark of Byrsonima japurensis A. Juss. (Malpighiaceae) are widely used as an anti-inflammatory drug in folk medicine of Amazonas State (Brazil). AIM OF THE STUDY: To evaluate the pharmacological potential of an aqueous extract of the stem bark of Byrsonima japurensis (BJEA) to scientifically verify of its traditional use. MATERIALS AND METHODS: Anti-inflammatory, antihyperalgesic and antiulcer activities were evaluated in Wistar rats, a Hippocratic screening was performed in Swiss mice to evaluate the toxic effects, and antiplatelet evaluation was performed in human platelet rich plasma assay. Additionally, antioxidant activity was evaluated by superoxide radical scavenging method and ß-carotene bleaching test. RESULTS: Anti-inflammatory, antihyperalgesic and gastroprotective activities were observed in rats treated orally with different doses of BJEA. While signals of toxicity were observed in the mice treated with a very high dose of extract (5000mg/kg), no death occurred. BJEA also showed expressive antiplatelet and antioxidant activities in vitro. CONCLUSION: According to our results, it was concluded that stem bark of Byrsonima japurensis has significant and safe anti-inflammatory activity, which is closely related with their potent antioxidant activity, supporting the folk medicinal use of this species.

Cardiac evaluation after experimental intoxication by Amorimia rigida (Malpighiaceae) extracts in rabbits

Clinical and laboratory changes were evaluated in rabbits after intoxication by Amorimia rigida, a plant that causes sudden death. Nine New Zealand male rabbits, averaging 3.54 kg, were categorized into three groups (n = 3) and received, for eight consecutive days, the equivalent of 30 g/kg dry matter of A. rigida water-soluble (SG) and water-insoluble (IG) extracts via nasoesophageal route. The control group received water. There were no alterations in creatine kinase enzyme (CK), CK myocardial fraction (CKMB) or troponine I (cTnI). None of the animals had clinical or electrocardiographic (conventional and Holter) alterations. There were progressive decreases in the left ventricular ejection fraction and systolic fractional shortening. Doppler echocardiography alterations suggested a systolic dysfunction in the SG and IG groups and diastolic dysfunction in IG group. It was concluded that the soluble and insoluble extracts of A. rigida cause deficit of cardiac function.

Aborto em bovinos devido à intoxicação por Tetrapterys acutifolia (Malpighiaceae) / Abortion in cattle due to Tetrapterys acutifolia poisoning

Esse estudo teve por objetivo demonstrar experimentalmente que Tetrapterys acutifolia Cav. (fam. Malpighiaceae) é capaz de provocar aborto em bovinos e caracterizar as alterações clínico-patológicas nas vacas e nos fetos. Estas plantas são responsáveis por significativo número de mortes em bovinos com mais de um ano de idade, especialmente nos Estados de Rio de Janeiro e São Paulo, mas até agora não havia sido comprovado experimentalmente seu efeito abortivo em bovinos. Os experimentos foram realizados no município de Barra do Piraí, RJ. Quatro vacas de descarte receberam brotos e folhas novas frescas de T. acutifolia, coletadas em propriedades vizinhas, nas doses de 2,5g/kg/dia, 5,0g/kg/dia (2 vacas) e 10g/kg/dia, até ocorrer o abortamento. O quadro clínico nas vacas caracterizou-se por arritmia cardíaca, tremores musculares, anorexia, ascite, jugular ingurgitada, edema de peito e barbela e aborto (23-76 dias após o início da ingestão da planta); todas as vacas abortaram. Das quatro vacas apenas uma (a que recebeu 10g/kg/dia) morreu 36 dias após o abortamento, com sintomas de insuficiência cardíaca. O exame necroscópico dos fetos/natimortos revelou hidrotórax, hidropericárdio, hidroperitônio e congestão hepática; ao corte do miocárdio, verificaram-se áreas pálidas. No exame histológico havia edema intersticial com fibrose incipiente. Na vaca que recebeu a maior dose e foi a óbito, bem como em outra intoxicada naturalmente, os achados de necropsia foram similares aos observados nos fetos, exceto pela dilatação dos vasos da base do coração e mais acentuada palidez do miocárdio. Observaram-se ainda edema subcutâneo nas regiões cervical e esternal, bem como veias jugulares ingurgitadas. Os achados histopatológicos foram necrose e edema intersticial com acentuada fibrose no miocárdio, espongiose da substância branca do encéfalo e, no fígado, congestão e leve fibrose. Adicionalmente, observou-se na vaca intoxicada espontaneamente, 17 dias após o aborto, arritmia cardíaca, jugular ingurgitada, edema de peito e barbela, anorexia com morte 43 dias após o aborto. Este estudo demonstra que Tetrapterys acutifolia é capaz de induzir aborto e, dependendo da dose, ainda causar a morte das vacas que abortarem.

Tetrapterys acutifolia Cav. (fam. Malpighiacae) stands out among the most important toxic plants of the Brazilian Southeast Region. These plants are responsible for a significant number of deaths in over 1-year-old cattle, especially in the states of Rio de Janeiro and São Paulo. This study aims to demonstrate that T. acutifolia is also able to induce abortion in cattle and to characterize the clinic-pathological alterations in cows and fetuses. Four cows, kept on pasture were used in the experiments which were performed on a farm in the county of Barra do Piraí, RJ, Brazil. The sprouts and young leaves of T. acutifolia were collected from the vicinity shortly before disposed in a trough. The experimental cows ingested the plant material at doses of 2.5g/kg/day (one cow), 5g/kg/day (two cows) and 10g/kg/day (one cow) until abortion occurred. All four cows aborted. The cows showed cardiac arrhythmia, muscular tremors, anorexia, ascites, distended jugular veins, edema of the sternal region and dewlap, and abortion (23 to 76 days after the beginning of ingestion of the plasnt) from the 5th to the 28th day of the experiment. Only one cow which received 10g/kg/day died with characteristic signs of heart failure, 36 days after she had aborted. Gross examination of the fetuses revealed hydrothorax, hydropericardium, hydroperitoneum, nutmeg appearance of the liver, few petechiae and ecchymoses in the epicardium, and pale areas in cross sections of the myocardium. The main postmortem findings in the cow that died were hydrothorax, hydropericardium and hydroperitoneum, engorged vessels at the heart base, exceedingly pale heart muscle with marked spots and stripes in cross sections. Distended jugular veins and severe edema in the sternal region and the abdominal wall were also observed. Histological examination of the fetal hearts revealed interstitial edema with incipient fibrosis and degenerative/necrotic changes of the myocytes. In the succumbed cow was found interstitial fibrosis, as well as necrotic areas and/or necrosis of individual myocytes in extensive portions of the heart, besides passive congestion of the liver. This study shows that Tetrapterys acutifolia can induce abortion in cattle and, depending on the dosage, can cause death.

Antidepressant effect and pharmacological evaluation of standardized extract of flavonoids from Byrsonima crassifolia.

Byrsonima crassifolia (Malpighiaceae) has been used in traditional medicine for the treatment of some mental-related diseases; however, its specific neuropharmacological activities remain to be defined. The present study evaluates the anxiolytic, anticonvulsant, antidepressant, sedative effects produced by the extracts of Byrsonima crassifolia, and their influence on motor activity in ICR mice. Additionally, we determine the acute toxicity profiles of the Byrsonima crassifolia extracts and the presence of neuroactive constituents. Our results show that the methanolic extract of Byrsonima crassifolia produces a significant (P<0.05) antidepressant effect in the forced swimming test in mice at 500 mg/kg dose. However, it does not possess anxiolytic, sedative, or anticonvulsant properties, and does not cause a reduction of mice locomotion (P>0.05). Although the main compound of the methanolic extract was identified as quercetin 3-O-xyloside (12 mg/kg), our findings suggest that flavonoids, such as rutin (4.4 mg/kg), quercetin (1.4 mg/kg) and hesperidin (0.7 mg/kg), may be involved in the antidepressant effects. To the best of our knowledge, the present study constitutes the first report on the presence of the flavonoids with neuropharmacological activity rutin and hesperidin in Byrsonima crassifolia. In conclusion, the present results showed that the methanolic extract standardized on flavonoids content of Byrsonima crassifolia possesses potential antidepressant-like effects in the FST in mice, and could be considered as relatively safe toxicologically with no deaths of mice when orally administered at 2000 mg/kg.

Mortes súbitas em bovinos causadas por Amorimia exotropica no Rio Grande do Sul / Sudden death in cattle due to the consumption of Amorimia exotropica (Malpighiaceae) in Rio Grande do Sul, Brazil

Descrevem-se casos de morte súbita em bovinos associados com a ingestão de Amorimia (Mascagnia) exotropica em seis propriedades rurais localizadas na região metropolitana de Porto Alegre e na serra gaúcha. Os bovinos intoxicados foram encontrados mortos sem história de sinais clínicos prévios, ou apresentaram tremores musculares, quedas bruscas, movimentos de pedalagem, opistótono, respiração ofegante e decúbito lateral, quando induzidos ao movimento poucos minutos antes da morte. Registrou-se maior número de casos entre os meses de maio e agosto. Nove bovinos foram necropsiados e os principais achados macroscópicos observados foram mucosa oral levemente cianótica (3/9), hidropericárdio leve a moderado (3/9), petéquias e equimoses no epicárdio (5/9), coágulo no interior do ventrículo esquerdo (4/9), edema pulmonar (5/9) e mucosas vermelhas no abomaso e no intestino delgado (6/9). Histologicamente havia necrose de coagulação no miocárdio (9/9) caracterizada por retração celular, aumento da eosinofilia do citoplasma com perda das estriações, vacúolos intracitoplasmáticos, núcleos em picnose, vacúolos intranucleares com marginalização da cromatina e ocasionais núcleos em cariorrexia e cariólise. No coração, edema intersticial (3/9) e infiltrado inflamatório intersticial predominantemente mononuclear (7/9) também foram observados. Nos rins de três bovinos havia degeneração hidrópico-vacuolar multifocal das células epiteliais dos túbulos contorcidos distais associada com núcleos picnóticos deslocados para periferia da célula.

Cases of sudden death in cattle were associated with the consumption of Amorimia (Mascagnia) exotropica and occurred in six ranches located in the mountainous region of Rio Grande do Sul and the metropolitan region of Porto Alegre, Brazil. Affected cattle were found dead with no history of previous clinical signs, or showed muscular tremors, falls, paddling, opistotonus, panting, and lateral recumbence after being induced to move, few minutes before death. Most cases were recorded between May and August. Nine cattle were necropsied and main gross findings were oral mucosae slightly cyanotic (3/9), mild to intermediate hydropericardium (3/9), epicardial petechiae and ecchymoses (5/9), clot within the left ventricle (4/9), lung edema (5/9), apart of abomasal and small intestinal reddened mucosa (6/9). Histologically, there was myocardial coagulation necrosis (9/9), which was characterized by cellular retraction, enhanced cytoplasmic eosinophilia, lack of cytoplasmic striations, intracytoplasmic vacuoles, nuclear piknosis, intranuclear vacuoles, chromatin marginalization and occasional nuclear karyorrhexis and karyolysis. There also were interstitial edema (3/9) and interstitial inflammatory infiltrate (mainly mononuclear) (7/9) in the heart, apart of multifocal vacuolar-hydropic degeneration in the epithelial cells of the distal convoluted tubules associated with pyknotic and eccentric nuclei in the kidneys of three cattle.

Poisoning by Amorimia (Mascagnia) sepium in sheep in northern Brazil.

The aim of this study was to determine the cause of sudden deaths in sheep in the Anari Valley of the state of Rondônia, in northern Brazil. In one outbreak, sheep were placed in an area where the owner had cut Amorimia (Mascagnia) sepium and let it dry for two days. Fourteen out of 35 sheep died with few outward clinical signs observed over a period of about 10 h after the ingestion of the dry plant. Dry A. sepium was administered experimentally to 9 sheep. Five died after the ingestion of single doses of 3-6.6 g/kg body weight (bw). Two sheep died after the ingestion of total doses of 6.4-31 g/kg bw over the course of 4 and 5 days, respectively, and one died after being treated with 33 daily doses of 0.56 g/kg bw. Six sheep died during exercise, and three died without exercise. Clinical signs were anorexia, muscular tremors, dyspnea, jugular engorgement, tachycardia, apathy, opisthotonos, foam in the nose, and recumbency. One sheep, which ingested a single dose of 1 g/kg bw, was not affected. The main macroscopic lesion was pulmonary edema. Histologic examination of the heart revealed degeneration and necrosis of cardiomyocytes, as well as multifocal inflammatory infiltrate of mononuclear cells. Fibrosis, neovascularization and infiltration by mononuclear inflammatory cells were observed in the sheep that ingested the plant for 33 days. Vacuolar-hydropic degeneration was observed in the epithelial cells of renal tubules of four sheep. It is concluded that A. sepium is responsible for sudden deaths in sheep.

Lesões perinatais em cordeiros induzidas pela administração de Tetrapterys multiglandulosa (Malpighiaceae) a ovelhas em diferentes estágios de gestação / Perinatal lesions caused in lambs by feedingTetrapterys multiglandulosa (Malpighiaceae) to sheep at different stages of their pregnancy

Foi realizada a intoxicação experimental em ovelhas em diferentes dias de gestação, 12 ovelhas foram dividas em quatro grupos. As ovelhas do Grupo 1 consumiram quatro doses de 5g/kg de folhas verdes durante quatro dias; ovinos do Grupo 2 consumiram duas doses de 10g/kg durante dois dias, o Grupo 3 consumiu uma dose de 20g/kg em um único dia e os ovinos do Grupo 4 não consumiram a planta (controle-negativo). Para testar a toxicidade da planta um ovino macho consumiu 5g/kg até manifestação dos sintomas. Não foram observados sinais clínicos da intoxicação nas ovelhas, mas três cordeiros tiveram morte perinatal, e um cordeiro morreu com três meses de idade; o ovino controle-positivo morreu após 38 dias de consumo diário da planta e os sinais clínicos foram taquipnéia, taquicardia, sonolência, incoordenação e fraqueza. Todos os quatro cordeiros e o ovino controle-positivo foram necropsiados e os achados de necropsia foram áreas esbranquiçadas no miocárdio, evidenciação do padrão lobular do fígado, pulmão vermelho enegrecido e rúmen acentuadamente distendido com presença de gases livres. Os achados histopatológicos foram fibrose cardíaca, necrose dos cardiomiócitos, congestão e edema pulmonar, congestão hepática centrolobular e degeneração esponjosa na região subcortical do encéfalo. Tetrapterys multiglandulosa demonstrou ser tóxica para os fetos ovinos em dosagens que não foram suficientes para induzir sinais clínicos nas ovelhas prenhes, e que a intoxicação pode ocorrer com morte de cordeiros logo após o parto, mesmo após meses de ter cessada a ingestão da planta.

In order to verify the effects of non-lethal doses of Tetrapterys multiglandulosa on ovine fetuses, experimental poisoning in sheep at different days of pregnancy was performed. Green leaves of shooting plants were administered to 9 pregnant ewes divided into three experimental groups. Sheep from Group 1 received four doses of 5g/kg of fresh leaves for 4 days; those from Group 2 received 10g/kg for 2 days; Group 3 sheep received a dose of 20g/kg for one day, and sheep from Group 4 did not receive the plant and served as negative controls. To check the plant toxicity, a male sheep (positive control) received 5g/ kg until the onset of clinical signs. No signs of poisoning were observed in pregnant ewes; three lambs died 1-5 days after birth, and a fourth lamb died within 3 months after have been born. The positive control died after 38 days of daily consumption of the plant, presenting tachypnea, tachycardia, drowsiness, incoordination, weakness and sudden death. All four dead lambs and the positive control sheep were necropsied. The gross lesions were whitish areas in the myocardium, increased lobular pattern of the liver, dark red lungs, metabolization of pericardial fat, and ruminal distention with free gas. Histological findings were cardiac fibrosis, cardiomyocyte necrosis, pulmonary congestion and edema, and spongy degeneration in subcortical cerebral white matter. Tetrapterys multiglandulosa resulted toxic for ovine fetuses at doses that were not suffient to induce clinical signs in the pregnant ewes, demonstrating that the poisoning may be a cause of death of lambs soon after birth, even several months after the ingestion of the plant has been discontinued.

Conditioning taste aversion to Mascagnia rigida (Malpighiaceae) in sheep.

The objective of this study was to determine if sheep could be averted to Mascagnia rigida, a toxic plant found in the semiarid region of northeastern Brazil. Twelve female sheep naïve to M. rigida were randomly allocated to two treatment groups: control (treated with 15 mL water orally by a drenching gun) and lithium group (treated with 150 mg LiCl/kg body weight orally by a drenching gun). For conditioning, sheep were allowed to feed on M. rigida leaves for 15 min, followed by LiCl or water administration. The time spent eating M. rigida leaves was measured. The conditioning was repeated daily until the LiCl-treated sheep stopped eating M. rigida, which occurred at days 2 and 3. Persistence trials were conducted on day 10, 24, 40, 55, and 70 of the trial using single-choice tests. There was no difference between the two treatment groups with respect to the consumption of M. rigida on the first day of aversion conditioning. On the second day, three out of the six sheep in the lithium group did not eat the leaves, but on the third day, all the sheep in the lithium group did not ingest M. rigida. This aversion persisted throughout all the persistence trials. This indicates that sheep can be easily conditioned by using lithium chloride to avoid eating M. rigida.

Perfis eletrocardiográfico e ecodopplercardiográfico de ovinos após ingestão da suspensão aquosa de Mascagnia rigida Griseb. (Malpighiaceae) / Electrocardiographical and echocardiographical profiles in experimental Mascagnia rigida Griseb. (Malpighiaceae) toxicosis in sheep

Estudou-se o perfil eletrocardiográfico e ecodopplercardiográfico de ovinos intoxicados experimentalmente pela Mascagnia rigida Griseb (Malpighiaceae). Quinze ovinos machos da raça Santa Inês, com sete meses de idade e pesando, em média, 27kg, foram distribuídos em três grupos (G) com cinco animais cada: No G1 (controle), os animais receberam apenas água; nos G2, receberam 20g/kg de M. rigida durante três dias; e no G3, 20g/kg de M. rigida, durante sete dias. As folhas de M. rigida foram trituradas com água e administradas na forma de suspensão, por via oral, por meio de sonda. M. rigida promoveu aumento da FC em repouso e, principalmente, durante o esforço físico e diminuiu a fração de ejeção e o percentual de encurtamento sistólico do ventrículo esquerdo.

The electrocardiographical and echocardiographical alterations produced by intraruminal administration of Mascagnia rigida griseb. (Malpighiaceae) in sheep were studied. Fifteen male Santa Inês sheep were randomly allotted to three groups: G1 - animals only received water (control); G2 - animals were treated with M. rigida, 20g/kg/day, for three days; and G3 - animals were treated with M. rigida, 20g/kg/day, for seven days. All treatments were administered by an orogastric tube. M. rigida administration produced increase in heart rate during rest and exercise, and decreased in fractional ejection, and fractional shortening.