Clinical and laboratory findings in sheep experimentally poisoned by Palicourea marcgravii and the use of magnesium chloride with possible therapeutic effect on poisoning / Achados clínicos e laboratoriais em ovinos experimentalmente intoxicados por Palicourea marcgravii e o uso do cloreto de magnésio com possível efeito terapêutico na intoxicação

This study aimed to examine the efficacy of magnesium chloride therapy in sheep experimentally poisoned by Palicourea marcgravii and describe the clinical and laboratory findings that may aid in early ante mortem diagnosis of this poisoning. P. marcgravii is an important plant within a group of 22 species in Brazil that cause "sudden death." Its toxic component is sodium monofluoroacetate. It was observed that a time for evolution of poisoning was longer in our study compared to other studies that used the same dose of P. marcgravii in sheep. However, all animals that were poisoned and subsequently treated with magnesium chloride died. The sheep presented characteristic clinical signs before death in addition to other signs that have not been previously described for this type of poisoning, such as abdominal breathing, coughing, head pressing, and nystagmus. This is the first evaluation of hematological parameters of sheep poisoned by P. marcgravii. Leukocytosis with neutrophilia, hyperfibrinogenemia, and hyperglycemia, associated with hypophosphatemia and elevated levels of serum aspartato aminotransferase (AST), glutamate dehydrogenase (GLDH), urea, creatinine, creatine kinase (CK) and lactate dehydrogenase (LDH), were observed. Additionally, changes were noted in necropsy, such as engorged jugular, large vessel congestion, pulmonary edema. Histological examination revealed vacuolar hydropic degeneration in the distal twisted uriniferous tubules in the kidneys, similar to those reported in previous studies on P. marcgravii poisoning.(AU)

O presente estudo objetivou verificar a eficácia terapêutica do cloreto de magnésio em ovinos intoxicados experimentalmente por Palicourea marcgravii e descrever os achados clínicos e laboratoriais que possam auxiliar no diagnóstico precoce ante mortem dessa intoxicação. P. marcgravii é a principal planta dentro de um grupo de 22 espécies que causam "morte súbita" no Brasil e seu princípio tóxico é o monofluoracetato de sódio. Durante o procedimento, observou-se maior tempo de evolução em relação a outros trabalhos utilizando-se a mesma dose da P. marcgravii em ovinos, entretanto todos os animais intoxicados e posteriormente tratados com cloreto de magnésio vieram a óbito. Os ovinos apresentaram sinais clínicos característicos antes da morte, associados a sinais nunca antes descritos nesse tipo de intoxicação, como respiração abdominal, tosse, "head pressing" e nistagmo. Trata-se da primeira avaliação dos parâmetros hematológicos de ovinos intoxicados por P. marcgravi. Foi observado leucocitose com neutrofilia, hiperfibrinogemia e hiperglicemia, associado a elevação dos valores séricos de AST, GLDH, ureia, creatinina, CK, LDH e hipofosfatemia. À necropsia foram notadas alterações como jugular ingurgitada, congestão de grandes vasos, edema pulmonar. Histologicamente havia degeneração hidrópica vacuolar nos túbulos uriníferos contorcidos distais no rim, semelhantes às já relatadas em estudos anteriores, na intoxicação por P. marcgravii.(AU)

Poisonous plants for ruminants in the dairy region of Pernambuco, Northeastern Brazil / Plantas tóxicas para ruminantes na bacia leiteira de Pernambuco, Nordeste do Brasil

A survey carried out in the dairy region of Pernambuco was conducted to determine the most important poisonous plants for ruminants in the region. A total of 95 farmers from 19 municipalities were interviewed and the grazing areas of ruminants were inspected. According to the survey, the most important poisonous plants for ruminants were Manihot esculenta, Palicourea aeneofusca, Brachiaria decumbens, Indigofera suffruticosa, Ricinus communis and Cestrum axillare. Less reported classes of poisonous plants included nephrotoxic plants and plants that cause abortions or congenic malformations. Psychotria hoffmannseggiana, Psychotria colorata and Psychotria capitata were reported by farmers as the cause of sudden death in cattle. These plants should be better investigated to evaluate their importance as the cause of cattle deaths.(AU)

Neste estudo prospectivo, realizou-se um levantamento sobre a ocorrência das principais plantas tóxicas e a ocorrência de intoxicações por plantas em ruminantes na bacia leiteira de Pernambuco. Para isso, foram entrevistados 95 produtores rurais de 19 municípios e as áreas de pastagem de ruminantes foram inspecionadas. De acordo com o levantamento, as plantas tóxicas mais importantes para ruminantes foram Manihot esculenta, Palicourea aeneofusca, Brachiaria decumbens, Indigofera suffruticosa e Ricinus communis. As classes menos importantes de plantas tóxicas incluíram plantas nefrotóxicas e plantas que causam abortos e malformações congênitas. Psychotria hoffmannseggiana, Psychotria colorata e Psychotria capitata foram relatadas por produtores rurais como a causa de mortes súbitas em bovinos. Essas plantas devem ser investigadas melhor para avaliar sua importância como a causa de mortes de bovinos.(AU)

Evaluation of the resistance of Nellore, Curraleiro Pe-duro and Pantaneiro cattle breeds by experimental intoxication of Palicourea marcgravii.

Palicourea marcgravii is the most important toxic plant in Brazil due to its acute toxicity (sudden death), palatability, cumulative effect and broad geographical distribution. The study aimed to evaluate the resistance between cattle of different breeds by experimental intoxication of Palicourea marcgravii. Eighteen males were randomly divided into three groups (Nellore, Curraleiro Pe-Duro and Pantaneiro), six animals in each group. All animals were experimentally intoxicated with P. marcgravii at 0.5 mg/kg of equivalent sodium monofluoracetate acid, receiving one single oral dose. All cattle presented symptoms and the toxic plant caused death in all cattle of the Nellore and Pantaneiro breeds and only three Curraleiro cattle. No changes were observed in the leukogram, fibrinogen, albumin, total protein and bilirubins. Hyperglycemia and increased of aspartate transaminase, creatinine kinase, urea and creatinine were detected in all breeds. Changes in the values of the gamma glutamyl transferase were individualized and did not follow a standard response. Fourteen cattle presented the histopathological findings of renal hydropic degeneration. The lower death rate of Curraleiro cattle indicates a higher resistance than cattle of the Nellore and Pantaneiro breeds.

Sequential administrations of trifluoroacetate induce tolerance to Palicourea maccgravii, a monofluoroacetate-containing plant, in calves.

Monofluoroacetate (MFA) is considered one of the most toxic substances known. It is found naturally in plants, and causes sudden death syndrome in ruminants. Due to hyperacute evolution of poisoning and the absence of effective treatment, induction of resistance in animals might be the best tool to control MFA poisoning in ruminants. The objective of this study was to promote resistance in cattle against the toxic effects of MFA through its degradation by the ruminal microbiota after the administration of sodium trifluoroacetate (TFA). Ten calves were distributed into two groups: control group (n = 3) and treated group (n = 7). The calves in the treated group received 0.1 mg/kg live weight of TFA, whereas, those in the control group received water; both for 28 consecutive days. The calves were subjected to daily clinical evaluation and weekly blood biochemical determination to identify any signs of poisoning. After 28 d of administration of TFA or water, 2.0 g/kg body weight of Palicourea marcgravii leaves (containing 0.15% MFA) were administered using a stomach tube to determine the occurrence of resistance. The administration of TFA did not induce any clinical or biochemical changes in blood. The administration of P. marcgravii induced clinical changes in the calves of control group, but there was no change in the calves of the treated group. In conclusion, the administration of TFA to cattle can induce effective resistance against MFA poisoning.

Combinational effects of non n-Hexane Fractions of ant-plant (Myrmecodia tuberosa Jack) hypocotyl with doxorubicin against lymphocyte and cancer cells.

Doxorubicin is widely used as a chemotherapeutic drug despite having many side effects. It may cause the dysfunction of macrophage, decreasing proliferation of lymphocytes, decreasing CD4+/CD8+ ratio and inducing hepatotoxicity. Doxorubicin inhibits the growth of Vero, HeLa, and T47D cell lines, and also induces a resistance of MCF-7 cells. Previous studies showed that ethanolic extract and ethyl acetate fraction of ant-plant (Myrmecodia tuberose Jack) hipocotyl could increase macrophage phagocytosis activity and lymphocyte proliferation in vitro. Therefore, antplant is a potential immune stimulator. Combinational treatment of non n-hexane fraction (NHF) of ant-plant with doxorubicin did not affect the doxorubicin's potency. Nevertheless, increased lymphocyte viability induced by doxorubicin in varied dosages of NHF that lethal to HeLa, MCF-7 and T47D cells. Moreover, on Vero cells, doxorubicin became less toxic when induced together with NHF. Thus, NHF of ant-plant is potential to be proposed as doxorubicin co-chemotherapeutic agent against cancer cells.

Acute and subacute toxicity of the aqueous extract of Alibertia edulis (Rich.) A. Rich. ex DC. in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Alibertia edulis, popularly known as "marmelo do Cerrado" is a native plant from the brazilian Cerrado. It has high food and ornamental potential and the tea leaves are currently used as hypoglycemic, antihypertensive and diuretic. AIM OF THE STUDY: In order to evaluate the safety of the aqueous extract of Alibertia edulis leaves (AEAE), the acute and subacute toxicity tests were performed in male and female Wistar albino rats. MATERIALS AND METHODS: The experiments were performed in accordance with the OECD guidelines 425 and 407. For the acute toxicity, one single dose of the AEAE (2000mg/kg) was administered by gavage to five female rats. The animals were observed for 14 days for any signs of toxicity and death. In the subacute toxicity, four different doses (125, 250, 500 and 1000mg/kg) of the AEAE were administered to male and female rats for 28 consecutive days. A satellite group received the maximum dose (1000mg/kg) for 28 days and remained untreated for 14 more days in order to observe reversibility, persistence, or delayed occurrence of toxic effects. The five parameters of the Hippocratic screening, body weight, food and water intake were daily observed. At the end of the experiment, blood samples were collected for the hematological and biochemical analysis. The vital and reproductive organs were inspected for any histopathological changes. RESULTS: No deaths or behavioral changes were observed during both experiments as well as no changes on organ weights, biochemical, hematological and histopathological parameters that could indicate any signs of toxicity. CONCLUSION: All doses tested can be considered safe in rats and the LD50 is higher than 2000mg/kg. Therefore, further assessments are required in order to proceed to clinical studies in humans.

Sinais clínicos e patologia da intoxicação crônica experimental de caprinos por palicourea marcgravii / Clinical signs and pathology of chronic experimental poisoning by palicourea marcgravii in goats

Palicourea marcgravii é considerada a principal planta tóxica de interesse pecuário no Brasil, porém, até o momento, é conhecido apenas o quadro agudo da intoxicação. Esse estudo avaliou as alterações clínico-patológicas de 10 caprinos cronicamente intoxicados por P. marcgravii. Os animais receberam, diariamente, 0,2g/kg de peso corporal da planta fresca por 6 a 38 dias. Os caprinos apresentaram como principais sinais clínicos anorexia, apatia, taquicardia, arritmia, pulso venoso jugular positivo e decúbito. Nas necropsias, os achados macroscópicos foram hidropericárdio, palidez dos rins e do miocárdio, atrofia gelatinosa da gordura cardíaca, evidenciação do padrão lobular hepático e edema pulmonar. Os principais achados microscópicos foram tumefação e vacuolização de cardiomiócitos, necrose de fibras cardíacas e infiltrado inflamatório mononuclear no miocárdio. Nos rins foi encontrada marcante degeneração hidrópico-vacuolar difusa. Os achados demonstraram nos caprinos cronicamente intoxicados, quadro clínico-patológico com características distintas do observado na forma aguda da intoxicação por P. marcgravii. Essas observações comprovam o risco para caprinos da ingestão da planta, mesmo que em pequenas doses, resultando no surgimento de quadro clínico e graves lesões ainda pouco conhecidas, e que poderiam ser confundidas com outras enfermidades.

Palicourea marcgravii is considered the main toxic plant for livestock in Brazil, however, only the acute intoxication has been reported. This study reports the clinical and pathological changes of 10 goats chronically intoxicated by P. marcgravii. The animals received, daily, 0.2g/kg body weight of the fresh plant during 6 to 38 days. The main clinical signs were anorexia, lethargy, tachycardia, arrhythmia, positive jugular venous pulse and recumbency. At necropsies, the lesions were pale kidneys and myocardium, serous atrophy of cardiac fat, evident hepatic lobular pattern and pulmonary edema. The main microscopic findings were swelling and vacuolization of cardiomyocytes, cardiac necrosis and inflammatory mononuclear infiltrate of the myocardium. The kidneys showed diffuse vacuolar hydropic degeneration of the epithelium. These findings demonstrated that goats chronically intoxicated by P. marcgravii show distinct clinicopathologic features than those observed in the acute form of the poisoning. It is suggested that goats may be spontaneously become intoxicated by the ingestion of small repeated doses of the plant and that the poisoning can be confused with other diseases.

Resistência à intoxicação por amorimia septentrionalis em caprinos, induzida pela inoculação ruminal das bactérias pigmentiphaga kullae e ancylobacter dichloromethanicus / Resistance to poisoning by amorimia septentrionalis in goats induced by ruminal inoculation of the bacteria pigmentiphaga kullae and ancylobacter dichloromethanicus

No Brasil, estima-se que as intoxicações por plantas tóxicas que contém monofluoroacetato de sódio (MFA) causam a morte de aproximadamente 500.000 bovinosao ano. A inoculação ruminal de bactérias que degradam MFA tem sido proposta como uma forma de prevenir a intoxicação. O presente trabalho teve como objetivo avaliar, em caprinos, a resistência ao MFA presente em Amorimia septentrionalis, induzida por inoculação ruminal das bactérias Pigmentiphaga kullae e Ancylobacter dichloromethanicus. Doze caprinos, que nunca tiveram contato prévio com plantas que contêm MFA, foram divididos em dois grupos, com seis animais cada. No grupo 1, 60 mL de uma mistura das duas bactérias foi inoculada, diariamente, durante 10 dias em cada caprino. No grupo 2, os caprinos não receberam as bactérias. A partir do 10º dia de inoculação, A. septentrionalis foi administrada, diariamente, na dose de 5g/kg de peso vivo, sendo interrompida em cada animal após a observação dos primeiros sinais clínicos da intoxicação. Os caprinos do grupo 1 apresentaram sinais clínicos 5,83±2,56 dias após a administração da planta o que diferiu significativamente (p=0,037) dos caprinos do grupo 2, que apresentaram sinais clínicos aos 2,67±0,52 dias. A quantidade de planta ingerida pelos caprinos inoculados (28,83±12,97g/kg) e os não inoculados (12,03±3,65g/kg) para desencadear os sinais clínicos foi, também, estatisticamente diferente entre os grupos (p=0,025). Conclui-se que a administração intraruminal de Pigmentiphaga kullae e Ancylobacter dichloromethanicus induz resistência à intoxicação por plantas que contêm MFA.

In Brazil is estimated that poisoning of livestock by sodium monofluoroacetate (MFA) containing plants causes the death of about 500.000 cattle per year. The ruminal inoculation of bacteria that degrade MFA has been proposed as a way to prevent the poisoning. This study aimed to evaluate in goats resistance to the MFA-containing plant Amorimia septentrionalis induced by ruminal inoculation of the bacteria Pigmentiphaga kullae and Ancylobacter dichloromethanicus. Twelve goats, without previous contact with MFA-containing plants, were divided into two groups of six animals each. In group 1, 60ml of a mixture of the two bacteria was inoculated every day for 10 days into each goat. In group 2, the goats did not receive the bacteria. At the 10th day of inoculation, A. septentrionalis began to be administered daily at a dose of 5g/kg body weight to both groups. The administration was interrupted in each goat after first clinical signs of poisoning were observed.. The goats of group 1 showed clinical signs 5.83±2.56 days after the administration of the plant, what differed significantly (p=0.037) from goats of group 2, that showed clinical signs 2.67±0 52 days after the beginning of ingestion. The amount of A. septentrionalis ingested by inoculated goats (28.83±12.97g/kg) to cause clinical sings was significantly greater (p=0.025) than the amount ingested by the non-inoculated (12.03±3.65) goats to cause clinical signs and was also statistically different between the groups. We concluded that the intraruminal administration of Pigmentiphaga kullae and Ancylobacter dichloromethanicus increases the resistance to poisoning by MFA-containing plants.

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.

Indução de resistência à intoxicação por Palicourea aeneofusca (Rubiaceae) mediante administração de doses sucessivas não tóxicas / Induction of resistance to Palicourea aeneofusca (Rubiaceae) poisoning by the continuous administration of non-toxic doses

Com o objetivo de comprovar se doses não tóxicas repetidas de Palicourea aeneofusca (Müll. Arg.) Standl. criam resistência à intoxicação, 12 caprinos foram distribuídos aleatoriamente em dois grupos experimentais de seis animais cada. No Grupo 1 foi induzida resistência mediante a administração, durante quatro períodos alternados, de 0,02g/kg das folhas dessecadas de P. aeneofusca durante 5 dias, 0,02g/kg durante 5 dias, 0,03g/kg durante 5 dias e 0,03g/kg por mais 5 dias. Entre o primeiro e o segundo período de administração e entre o segundo e o terceiro período os animais não receberam planta por 10 dias consecutivos e entre o terceiro e quarto período de administração os animais permaneceram 15 dias sem ingerir a planta. Um caprino morreu subitamente quando estava recebendo 0,03 g/kg da planta, no terceiro período de administração. O Grupo 2 não foi adaptado ao consumo de P. aeneofusca. Quinze dias após a adaptação ao consumo de P. aeneofusca do Grupo 1, os dois grupos receberam P. aeneofusca na dose diária de 0,03g/kg durante 19 dias. A partir do 20º dia de administração continuada a dose diária de P. aeneofusca foi aumentada para 0,04g/kg. Esta dose foi administrada por mais 12 dias. Os animais que mostraram sinais clínicos foram retirados do experimento imediatamente após a observação dos primeiros sinais. Um caprino do Grupo 2 apresentou sinais clínicos de intoxicação e morreu no 12º dia de administração e dois apresentaram sinais clínicos no 24º dia; um se recuperou e outro morreu. Após finalizada esta fase do experimento e para comprovar se os caprinos que não tinham adoecido no Grupo 2 tinham também adquirido resistência, foi introduzido outro grupo com três caprinos. Esses três caprinos (Grupo 3), os cinco caprinos do Grupo 1 e os três sobreviventes do Grupo 2, ingeriram uma dose diária de 0,06g/kg. Os três caprinos do Grupo 3 adoeceram no terceiro dia após o início da ingestão, dois morreram em forma hiperaguda e o outro recuperou-se após 10 dias. Todos os caprinos dos Grupos 1 e 2 ingeriram P. aeneofusca na dose de 0,06g/kg/dia durante nove dias sem apresentar nenhum sinal clínico. Os resultados deste trabalho demonstram que a administração de doses não tóxicas repetidas de P. aeneofusca aumentam significativamente á resistência à intoxicação e que esta técnica poderia ser utilizada para o controle da intoxicação por P. aeneofusca e outras espécies de Palicourea com similar toxicidade. Os resultados de pesquisas anteriormente realizados sugerem que a resistência à intoxicação por plantas que contêm MFA é devida a proliferação de bactérias que degradam MFA no rúmen.

Palicourea aeneofusca (Müll. Arg.) Standl. is a toxic plant which contains sodium monofluoroacetate (MFA). With the objective to investigate if repeated non-toxic doses of P. aeneofusca induce resistance to the intoxication by this plant, 12 goats were distributed in two similar groups. In Group 1, resistance was induced by the administration of the dry plant, during four alternate periods: 0.02g/kg during 5 days, 0.02g/kg during 5 days, 0.03g/kg during 5 days, and 0.03g/kg during 5 days. Between the first and second period of administration and between the second and the third period, the goats did not ingest P. aeneofusca for 10 days. Between the third and the fourth administration period the goats did not ingest the plant during 15 days. One goat died suddenly during the third administration period when was ingesting 0.03g/kg. The goats from Group 2 were not adapted to the consumption of P. aeneofusca. Fifteen days after the end of the adaptation period in Group 1, both groups ingested dry P. aeneofusca in the daily dose of 0.03g/kg during 19 days. From day 20 the daily dose was increased to 0.04g/kg, which was ingested for 12 days. The goats that showed clinical signs were removed from the experiment immediately after the observation of first signs. One goat from Group 2 showed clinical signs of poisoning and died on the 12th day of ingestion, and two showed clinical signs on day 24th; one recovered and the other died. At the end of the 31 days administration period, a new group (Group 3) with three goats was introduced in the experiment to investigate if the goats that did not become poisoned in Group 2 had acquired resistance. The three goats from Group 1, five goats from Group 1, and three from Group 2 started to ingest a daily dose of 0.06g/kg of dry P. aeneofusca. On the third day of ingestion the three goats from Group 3 showed clinical signs. Two died suddenly and another recovered 10 days after the end of ingestion. All goats of Groups 1 and 2 ingested 0.06g/kg/day during nine days without showing clinical signs. These results demonstrated that non-toxic repeated doses of P. aeneofusca increase significantly the resistance to the poisoning, and that this technique possibly could be used to control the poisoning by P. aeneofusca or other toxic Palicourea species. The results of previous research work suggest that resistance is due to the proliferation of MFA degrading bacteria in the rumen.

Importância econômica, epidemiologia e controle das intoxicações por plantas no Brasil / Economic impact, epidemiology and control poisonous plants in Brazil

A importância econômica, epidemiologia e controle das intoxicações por plantas em animais domésticos no Brasil são revisadas. Com os dados dos laboratórios de diagnóstico de diferentes regiões do país, as perdas anuais por mortes de animais foram estimadas em 820.761 a 1.755.763 bovinos, 399.800 a 445.309 ovinos, 52.675 a 63.292 caprinos e 38.559 equinos. No Brasil, atualmente, o número de plantas tóxicas é de 131 espécies e 79 gêneros e aumenta permanentemente. No entanto, a maioria das perdas são causadas por poucas plantas, incluindo Palicourea marcgravii, Amorimia spp., Senecio spp., Pteridium aquilinum, Ateleia glazioviana e Cestrum laevigatum em bovinos, Brachiaria spp em bovinos e ovinos, Nierembergia veitchii, Mimosa tenuiflora e Ipomoea asarifolia em ovinos, plantas que contêm swainsonina (Ipomoea carnea, Turbina cordata e Sida carpinifolia) em caprinos e Brachiaria humidicola e Crotalaria retusa em equinos. Os principais fatores epidemiológicos relacionados às intoxicações por plantas incluem palatabilidade, fome, sede, facilitação social, desconhecimento da planta, acesso a plantas tóxicas, dose tóxica, período de ingestão, variações de toxicidade e resistência/susceptibilidade dos animais às intoxicações. Quanto aos métodos de controle e profilaxia descrevem-se os resultados obtidos no Brasil com métodos recentemente desenvolvidos, incluindo controle biológico, aversão alimentar condicionada, utilização de variedades não tóxicas de forrageiras, utilização de animais resistentes às intoxicações e técnicas de indução de resistência.

The economic impact, epidemiology and control of plant poisonings in Brazil are reviewed. With the data obtained from diagnostic laboratories from different Brazilian regions, annual losses due to animal deaths are estimated in approximately 820.761 to 1.755.763 cattle, 399.800 to 445.309 sheep, 52.675 to 63.292 goats, and 38.559 horses. In Brazil toxic plants include 131 species within 79 genera, but this number is increasing continuously. However, most economic losses are caused by few plants including Palicourea marcgravii, Amorimia spp., Senecio spp., Pteridium aquilinum, Ateleia glazioviana and Cestrum laevigatum in cattle, Brachiaria spp. in cattle and sheep, Nierembergia veitchii, Mimosa tenuiflora and Ipomoea asarifolia in sheep, swainsonine-containing plants (Ipomoea carnea, Turbina cordata and Sida carpinifolia) in goats, and Brachiaria humidicola and Crotalaria retusa in horses. The main factors that determine the occurrence and frequency of plant poisoning include palatability, hunger, thirst, social facilitation, unawareness of the plant, access to toxic plants, toxic dose, ingestion period, variations in toxicity, and animal resistance/susceptibility. The results obtained in Brazil with the use of biological control, conditioned food aversion, selection of non-toxic varieties of forages, use of resistant animals to poisoning, and techniques to induce resistance are described.

Efeito protetor da acetamida em bovinos indica monofluoroacetato como princípio tóxico de Palicourea marcgravii (Rubiaceae) / Protective effect of acetamide in cattle indicates that monofluoroacetate is the toxic principle of Palicourea marcgravii (Rubiaceae)

O presente trabalho teve como objetivo avaliar e comparar o efeito protetor da acetamida nas intoxicações experimentais por monofluoroacetato (MF) e por folhas frescas de Palicourea marcgravii em bovinos, no intuito de confirmar, de forma prática, que esse composto é o princípio tóxico responsável pelo quadro clínico-patológico e pela morte dos animais intoxicados por essa planta. Três bovinos receberam MF, por via oral, na dose de 0,5mg/kg e, em seguida, a dois desses animais administraram-se acetamida, por via oral, nas doses de 0,38 e 2,0g/kg. Outros dois bovinos receberam 1,0g/kg de P. marcgravii, em seguida, a um deles administrou-se 1,0 g/kg de acetamida. Acetamida, quando administrada em quantidades suficientes (maior dose), evitou o aparecimento dos sinais clínicos e a morte de todos os animais que receberam MF ou P. marcgravii. Tal efeito protetor foi, de fato, confirmado após uma semana, quando o mesmo protocolo experimental foi repetido, para cada bovino, porém sem a administração de acetamida. Todos os bovinos não tratados com acetamida manifestaram sinais clínicos e morreram subitamente. O quadro clínico-patológico manifestado pelos bovinos intoxicados por MF ou P. marcgravii foi semelhante e, caracterizou-se por "morte súbita". Os animais em geral, apresentaram taquicardia, taquipnéia, tremores musculares, jugular repleta com pulso venoso positivo, polaquiúria, instabilidade, perda de equilíbrio, por vezes, cambaleavam e apoiavam a cabeça no flanco. Na fase final, todos os animais deitavam-se e levantavam-se com maior frequencia, deitavam ou caíam em decúbito lateral, esticavam os membros, faziam movimentos de pedalagem, apresentavam respiração ofegante, arritmia, opistótono, nistagmo, mugiam e morriam. A duração da "fase dramática" variou de 2 a 26min. À necropsia verificaram-se, em geral, aurículas, jugulares, ázigos e pulmonares leve a moderadamente ingurgitadas, leve a acentuado edema da subserosa da vesícula biliar, sobretudo, na sua inserção no fígado, bem como moderada quantidade de líquido espumoso róseo na traquéia e brônquios. O exame histopatológico revelou, no rim de todos os animais, leve até acentuada degeneração hidrópico-vacuolar das células epiteliais dos túbulos uriníferos contornados distais associada à picnose nuclear; no fígado, havia leve a moderada congestão, discreta a moderada tumefação e moderada vacuolização de hepatócitos, predominantemente, centrolobular, necrose de coagulação individual ou de grupos de hepatócitos e corpúsculos de choque. Os dados obtidos neste trabalho comprovam, de forma prática, que MF é o princípio tóxico de P. marcgravii responsável pelo quadro clínico-patológico e a morte dos animais que ingerem e se intoxicam naturalmente por essa planta, uma vez que a acetamida atua como antídoto eficaz (efeito antagônico) de forma idêntica em ambas as intoxicações.

The aim of the study was to evaluate and compare the protective effect of acetamide in experimental poisoning by fresh leaves of Palicourea marcgravii and monofluoroacetate (MF) in catlle, in order to prove in a practical way that this compound is the toxic principle responsible for the clinical signs and death of animals that ingested the plant. MF was administered orally in single doses of 0.5mg/kg to three cows; a few minutes later, two of these cows received, orally, single doses of acetamide (0.38 or 2.0g/kg). Two other cows ingested 1.0g/kg of P. marcgravii, and one of these cows received some minutes later 1.0g/kg of acetamide. Adequate doses of acetamide, administered right after the poisoning by P. marcgravii or MF, were able to prevented the onset of clinical signs and avoid the death of all animals. One week later, the experiments were repeated, but without the antidote. All animals not treated with acetamide showed symptoms of poisoning and died suddenly. MF and P. marcgravii caused the same clinical and pathological picture of "sudden death" in cattle. Clinically, the cattle presented palpitation, abdominal breathing, muscle tremors, engorged jugular vein with positive pulse, pollakiuria, slight loss of balance with sometimes swaying gait, the animals laying down and with the head on their flank. In the "dramatic phase", all the animals fell into lateral decubitus, stretched the limbs, made paddling movements, presented opistotonus, arrhythmia, nystagmus, and died. The "dramatic phase" lasted from 2 to 26 minutes. At postmortem examination, the heart auricles, jugulars and pulmonary veins were slightly to moderately ingurgitated; slight to marked edema of the subserosa was seen in fixation sites of gall bladder to the liver. In one cow, pulmonary edema was observed. Histopathology revealed in all cows slight to marked hydropic-vacuolar degeneration of the epithelial cells of the distal convoluted uriniferous tubules associated with nuclear pyknosis. Coagulation necrosis of individual or groups of hepatocytes and slight to moderate hepatic congestion with numerous shock corpuscles were also observed. The experimental results showed in practice that MF is the toxic principle responsible for the clinical-pathological picture and death of the cattle that ingested P. marcgravii, since acetamide acts as an efficient antidote (antagonistic effect), identical in both poisonings.

In-vivo laxative and toxicological evaluation and in-vitro antitumour effects of Mitracarpus frigidus aerial parts.

OBJECTIVES: To evaluate the in-vitro antitumour properties, and the in-vivo laxative and toxicological effects of the methanolic extract of the aerial parts of Mitracarpus frigidus (MFM). METHODS: The in-vitro antitumour activity of MFM was evaluated against three human tumour cell lines: Jurkat, HL60 and MCF-7. The laxative activity and the effect of MFM on intestinal motility were evaluated in rats at the doses of 100, 300 and 1000 mg/kg. Acute oral toxicity was performed at 10, 100, 1000 and 2000 mg/kg and subchronic toxicity was evaluated at 100, 300 and 1000 mg/kg of MFM during a 42-day period. After subchronic administration of MFM the biochemical, haematological and histopathological parameters were analysed. Also, the total content of anthraquinones was determined. KEY FINDINGS: MFM was cytotoxic only against HL60 and Jurkat cells with 89 and 83% growth inhibition, respectively. The laxative activity of MFM was similar to bisacodyl. Regarding the effect on intestinal motility, MFM showed a significant increase in the pathway of charcoal compared with the group treated with saline. Furthermore, MFM showed no in-vivo toxicity at the doses tested. Free and anthraquinone C- and O-glycosides were detected in MFM. CONCLUSIONS: MFM showed significant antitumour activity for leukaemic cells. Moreover, it presented laxative potential and no in-vivo toxicity.

Endophytic bacteria in toxic South African plants: identification, phylogeny and possible involvement in gousiekte.

BACKGROUND: South African plant species of the genera Fadogia, Pavetta and Vangueria (all belonging to Rubiaceae) are known to cause gousiekte (literally 'quick disease'), a fatal cardiotoxicosis of ruminants characterised by acute heart failure four to eight weeks after ingestion. Noteworthy is that all these plants harbour endophytes in their leaves: nodulating bacteria in specialized nodules in Pavetta and non-nodulating bacteria in the intercellular spaces between mesophyll cells in Fadogia and Vangueria. PRINCIPAL FINDINGS: Isolation and analyses of these endophytes reveal the presence of Burkholderia bacteria in all the plant species implicated in gousiekte. Although the nodulating and non-nodulating bacteria belong to the same genus, they are phylogenetically not closely related and even fall in different bacterial clades. Pavetta harborii and Pavetta schumanniana have their own specific endophyte--Candidatus Burkholderia harborii and Candidatus Burkholderia schumanniana--while the non-nodulating bacteria found in the other gousiekte-inducing plants show high similarity to Burkholderia caledonica. In this group, the bacteria are host specific at population level. Investigation of gousiekte-inducing plants from other African countries resulted in the discovery of the same endophytes. Several other plants of the genera Afrocanthium, Canthium, Keetia, Psydrax, Pygmaeothamnus and Pyrostria were tested and were found to lack bacterial endophytes. CONCLUSIONS: The discovery and identification of Burkholderia bacteria in gousiekte-inducing plants open new perspectives and opportunities for research not only into the cause of this economically important disease, but also into the evolution and functional significance of bacterial endosymbiosis in Rubiaceae. Other South African Rubiaceae that grow in the same area as the gousiekte-inducing plants were found to lack bacterial endophytes which suggests a link between bacteria and gousiekte. The same bacteria are consistently found in gousiekte-inducing plants from different regions indicating that these plants will also be toxic to ruminants in other African countries.

Diuretic activity and acute oral toxicity of Palicourea coriacea (Cham.) K Schum.

AIM OF THE STUDY: Palicourea coriacea (Cham.) K Schum, is an endemic plant used in the Midwestern Region of Brazil, popularly known as "douradinha do campo" and "congonha do campo". This plant has been used in traditional medicine for several ailments, especially to treat kidney diseases. Since no formal studies on the biological activities and medicinal properties of the ethanolic extract of Palicourea coriacea (PCEE) have been carried out previously, the present study represents the first research into the efficacy of this plant as a diuretic agent employing laboratory rats as test animals. MATERIALS AND METHODS: For diuretic activity evaluation we assayed three doses of PCEE (20, 40 and 80mg/kg) and measurement of the urinary volume and electrolytes (Na(+), K(+)) concentration were taken. The acute oral toxicity of PCEE was investigated according to OECD Guideline 423. RESULTS: The oral administration of a single dose of PCEE significantly increased the urinary volume in 24h. Additionally, the treatment with PCEE increased, in a dose-dependent manner, the excretion of both, Na(+) and K(+). No sign of toxicity was observed in the animals. CONCLUSIONS: The present study confirmed the ethnopharmacological use of Palicourea coriacea as a diuretic agent in the experimental condition tested here. Additionally, this work supports the importance of the preservation of local knowledge as well as the conservation of Brazilian biodiversity.

Mortes súbitas em bovinos causadas por Palicourea aeneofusca (Rubiaceae) e Mascagnia rigida (Malpighiaceae)na Zona da Mata Paraibana / Sudden deaths caused by Palicourea aeneofusca (Rubiaceae) and Mascagnia rigida (Malpighiaceae) in cattle in the Zona da Mata of Paraíba

Neste trabalho descrevem-se, em bovinos, um surto de intoxicação por Palicourea aeneofusca no município de Jacaraú e um surto de intoxicação por Mascagnia rigida, no município de Sapé. Ambos os surtos ocorreram na zona da Mata Paraibana, onde não havia, anteriormente, informação sobre intoxicação por plantas que causam mortes súbitas associadas ao exercício. A toxicidade de ambas as plantas frescas recém coletadas foi testada em coelhos, sendo a dose letal de 3g por kg de peso animal (g/kg) para P. aeneofusca e de 10g/kg para M. rigida. Na fazenda onde ocorreu o surto de intoxicação por P. aeneofusca foi encontrada, também M. rigida e o produtor informava que esta tinha causado, anteriormente, mortes de bovinos. M. rigida coletada nesta última fazenda foi tóxica na dose de 10g/kg da planta seca. Anteriormente a intoxicação por P. aeneofusca tinha sido diagnosticada na Zona da Mata e Agreste Pernambucano e leste da Bahia. Há também numerosos históricos da ocorrência desta intoxicação na Zona da Mata Alagoana, o que sugere sua ocorrência no litoral do nordeste, desde a Bahia até Paraíba. M. rigida é a planta tóxica mais conhecida e mais importante do nordeste ocorrendo no sertão e no agreste. Este trabalho comprova que, pelo menos na Paraíba, a intoxicação ocorre, também, na Zona da Mata.(AU)

This paper reports an outbreak of poisoning by Palicourea aeneofusca in cattle, in the municipality of Jacaraú, and another by Mascagnia rigida in the municipality of Sapé. Both outbreaks occurred in the Zona da Mata of Paraíba, where there are no previous reports of poisoning by toxic plants causing sudden death associated to exercise. The toxicity of both plants was tested in rabbits. The lethal dose was of 3g per kg body weight (g/kg) for fresh P. aeneofusca and 10g/kg for fresh Mascagnia rigida. On the farm where the poisoning by P. aeneofusca was observed, M. rigida also was found. The farmer reported that this plant also caused sudden death previously. M. rigida collected on that farm and given dried to rabbits caused death at the dose of 10gkg. The poisoning by P. aeneofusca in cattle had been previously reported in the Zona da Mata and Agreste of Pernambuco and east of Bahia. There are also numerous farmers' reports about the occurrence of the poisoning in the Zona da Mata of Alagoas, suggesting that it occurs in the whole coastal region, from Bahia to Paraíba. M. rigida is the most important toxic plant for cattle in the Brazilian semiarid. The results of this paper demonstrate that this plant poisoning also occurs in the tropical wet climate of the Zona da Mata.(AU)

Calcium oxalate crystals and methyl salicylate as toxic principles of the fresh leaves from Palicourea longiflora, an endemic species in the Amazonas state.

The species of the genus Palicourea (Rubiaceae family) is well-known for its toxicity towards animals, particularly livestock. This work reports the occurrence of skin irritation during the manipulation of Palicourea longiflora, considering the prevalence of the monofluoracetic acid (MFAA) and another toxic compound: methyl salicylate. The MFAA was identified by 19F-NMR and methyl salicylate by gas chromatography linked to mass spectrometry (GC/MS) analysis. Additionally, an anatomical study of leaves had been used to explain the mechanism of penetration of the toxic principles.

Efeitos farmacológicos e toxicológicos do extrato de Posoqueria acutifolia Mart. (Rubiaceae) em roedores / Pharmacological and toxic effects of Posoqueria acutifolia Mart. (Rubiaceae) extract in rodents

O presente trabalho investigou os efeitos farmacológicos e toxicológicos do extrato metanólico dos galhos de Posoqueria acutifolia. Foram realizados os testes de contorções abdominais, formalina, placa quente, edema de pata e pleurisia, bem como para a toxicidade aguda. As doses de 100, 200 e 400 mg/kg inibiram as contorções abdominais. No teste da formalina, a dose de 400 mg/kg reduziu o tempo de lambida da primeira fase, enquanto este efeito foi observado nas doses de 200 e 400 mg/kg sobre a segunda fase. O tempo de permanência sobre aplaca quente aumentou na dose de 400 mg/kg, embora a dose de 200 mg/kg também tenha tido efeito significativo após 90 minutos de tratamento. Houve uma redução do edema de pata, do volume do exsudato e da migração leucocitária nas doses testadas. O extrato testado não foi tóxico nas doses avaliadas. Portanto, o extrato metanólicode P. acutifolia exibe efeitos analgésico e antiinflamatório, o que poderia estar relacionado a seu uso na medicina popular

In the present study, the pharmacological and toxic effects on mice of methanol extract of branches of the Brazilian tree Posoqueria acutifolia were investigated. The tests carried out were acetic acid induced writhing, paw licking induced by formalin, hot plate, paw edema and pleurisy, as well as in acute toxicity test. Doses of 100, 200 and 400 mg/kg inhibited the abdominal contortions. In the formalin test, the first phase of paw licking was shortened at the dose of 400 mg/kg, while the second phase was significantly affected by 200 and 400 mg/kg. The time of reaction to the hot plate increased with 400 mg/kg, although 200 mg/kg had a significant effect after 90 min of treatment. All doses of the methanolic extract reduced the paw edema, the volume of the exsudate and the leukocyte migration. The tested extract showed low acute toxicity to mice. It was concluded that (or thus) the methanol extract of P. acutifolia branches possess analgesic and antiinflammatory activity, which could justify the popular medicinal application of this plant.

Analysis of the toxic potential of Palicourea corymbifera (Müll. Arg.) Standl. in laboratory animals.

Palicourea species may produce bovine toxicity. Palicourea corymbifera grows in terra firme forests within the Amazon rain forest and in Tropical America, particularly in spots that gave place to gazing areas. The lyophilized extract done with the aerial organs of P. corymbifera were analyzed in male and female mice. Results revealed a significant toxicity: LD50 was 1.10 (1.04-1.15)g/kg for male mice, and 1.05 (1.00-1.10)g/kg for female mice. Locomotion was affected as well as there were reflexes linked to environmental stimuli in addition to changes in posture. Progressive central nervous system stimulus signs such as trembling and convulsions were detected, the latter followed by the animal's death. Macroscopic histopathological exams performed on the liver, kidneys and lungs of mice submitted to necropsy did not indicate the existence of lesions. General activity of animals, measured in an open field, was reduced as a result of the administration of the extract. Duration of locomotion and rearing frequency were reduced, in opposition to an increase in the duration of immobility. Thin layer chromatography analysis showed that monofluoroacetic acid is present in the lyophilized extract, but other qualitative techniques as gas chromatography/mass spectrometry and 19F nuclear magnetic resonance showed that the MFAA was not present in the extract, and that the toxicity is related to other compound, although the toxic profile is very similar to that of MFAA. P. corymbifera was shown to be significantly toxic to laboratory animals and investigation of the possible toxic substance shall be done.

Estudo comparativo da toxidez de Palicourea juruana (Rubiaceae) para búfalos e bovinos / A comparative study of the toxicity of Palicourea juruana (Rubiaceae) to buffalo and cattle

O estudo foi realizado com os objetivos de estabelecer a sensibilidade dos búfalos a Palicourea juruana e agregar novos dados sobre a toxidez dessa planta para bovinos. Embora os quadros clínico-patológicos tenham sido semelhantes, a comparação das doses letais para búfalos (entre 1 e 2 g/kg) e para bovinos (0,25 g/kg) estabelece o búfalo como pelo menos quatro vezes mais resistente. Em experimentos realizados 10 anos antes - com amostras de P. juruana coletadas na mesma fazenda no Pará, em julho de 1993, início da época de seca, portanto apenas 2 meses mais tarde do que os agora realizados em maio de 2003 - a dose letal para bovinos foi de 2 g/kg. Não encontramos explicação para a toxicidade extremamente elevada da planta verificada nesse estudo.