In vivo and in vitro prospection of the anti-ophidic properties exercised by the extracts of Jacaranda decurrens L

The research and development of alternative treatments for snakebites (e.g., medicinal plants) is necessary due to the high costs of the existing ones. The effects of the aqueous extracts from Jacaranda decurrens leaves, roots, and xylopodium were analyzed upon the venom-induced (Bothrops spp. and Crotalus spp.) systemic and local toxicity. The extracts were able to partially inhibit the phospholipase activity of the venoms from Bothrops jararacussu and Crotalus durissus terrificus. The myotoxic, edema-inducing, coagulant, and hemorrhagic activities were also inhibited. The SDS-PAGE showed that the venom proteins were intact after their incubation with the extracts. This suggests that the possible mechanism of inhibition is not related to the degradation of the protein but rather to their binding to specific sites of the enzymes. The extracts significantly prolonged the survival time of animals in the lethality assay performed with Crotalus durissus terrificus venom and its toxin (crotoxin). The anti-ophidic activity of medicinal plants may aid in the management of snakebites in distant locations by reducing the victim’s local effects and time to heal.

Toxicity study of ethanol extract from Oroxylumindicum (L.) Vent in rats.

OBJECTIVE: To evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats. METHODS: Oroxylumindicum (L.) Vent extract was administrated to male and female rats by gavage once daily at doses of 54, 225, and450 mg?kg-1?d-1. The rats were sacrificed after administration for13 weeks and 26 weeks. Part of the rats in each group were allowed to recover for 4 weeks after 26-week administration. Systematic examinations including haematology, urology, blood biochemistry and histomorphology were performed at the end of 13, 26 weeks of administration and 4 weeks of recovery. RESULTS: No treatment related adverse effect shappened on rats'general status, body weight, food consumption, urinary index and histomorphology examination. Although during the administration, in some rats of extract's groups, the value of Red blood cell count (RBC), white blood cell counts (WBC), hemoglobin (HGB), haematocrit (HCT) and K iron were decreased, and biochemistry index, such as glucose (GLU), triglyceride (TG), alanine transaminase (ALT) and blood urea nitrogen(BUN) were increased, the above parameters were within the normal ranges and all returned to baseline after the drug stopping for 4 weeks. CONCLUSION: The administration of Oroxylumindicum(L.) Vent extractat levers up to 450 mg/kg (equals to 75 times of clinical dose) is well toleratedfor both genders without significant toxicity within the administration duration in this study.

Evaluation of acute and subacute toxicity of hydroethanolic extract of Dolichandra unguis-cati L. leaves in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dolichandra unguis-cati L. is a native climbing plant of Brazil, popularly known as "unha de gato". It has been traditionally used mainly as an antipyretic, anti-inflammatory and anti-tumor agent, yet little toxicological information is found in the literature. AIM OF THE STUDY: To identify the chemical composition of the hydroethanolic extract obtained from the leaves of Dolichandra uniguis-cati and to evaluate the acute and subacute toxicity in male and female rats, in order to assess the safety profile of this plant. MATERIALS AND METHODS: In the acute study, a single dose (2000mg/kg) of the extract was orally administered to male and female rats. In the subacute study, the extract was orally administered to male and female rats at doses 100, 200 and 400mg/kg for 28 days. Behavioral changes, catalase and tbars evaluations, biochemical, hematological and histopathological analysis were determined. The extract' chemical composition was accessed through UHPLC/MS. RESULTS: Chlorogenic acid, caffeic acid, ferulic acid, vanillinic acid, p-coumaric acid, rosmarinic acid, trans-cinnamic acid, luteolin, apigenin, quercitrin and quercetin were identified in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. In relation to the subacute study, females showed a reduction in AST (100, 200 and 400mg/kg), ALT (200mg/kg) and BUN (100 and 200mg/kg) levels, while male rats 400mg/kg presented an increase in AST levels. The Chol dosage significantly decreased in female rats in a dose-dependent manner, whereas for male rats this parameter showed no statistically significant reductions. No behavioral and histopathological changes were recorded. CONCLUSIONS: Our results indicate that the hydroethanolic extract of Dolichandra unguis-cati leaves did not present relevant toxic effects when administered orally to male and female rats. The extract also showed a potential hypocholesterolemic activity.

Studies in regard to the classification and putative toxicity of Fridericia japurensis (Arrabidaea japurensis) in Brazil.

Numerous plant species worldwide including Palicourea marcgravii (Rubiaceae) and Tanaecium bilabiatum (Bignoniaceae) in Brazil cause acute cardiac failure (sudden death) and are known to contain monofluoroacetate (MFA). Other Bignoniaceae species including Fridericia japurensis (Arrabidaea japurensis) are reported to cause sudden death in livestock in the Brazilian state of Roraima and are suspected to contain MFA due to the similarity of clinical signs. In this study herbarium specimens of Fridericia japurensis and field collections suspected to be F. japurensis were analyzed for MFA, and plant material from the field collections was dosed to rabbits. No MFA was detected in the herbarium specimens authoritatively identified as F. japurensis; however, MFA was detected in the field collections, which were identified as T. bilabiatum. Rabbits dosed orally with T. bilabiatum died acutely. Voucher toxic specimens initially described as F. japurensis were incorrectly identified, and the correct botanical name for this plant is T. bilabiatum (Arrabidaea bilabiata). Based on this study we conclude that there are no data to support the toxicity of F. japurensis and that the plant previously reported under this name as causing acute cardiac failure in cattle in Roraima is T. bilabiatum. This research highlights the importance of voucher specimens as part of any toxic plant investigation and corrects the literature regarding these toxic plants.

Fitotoxicidade da fase orgânica e do composto majoritário obtidos da polpa dos frutos de Crescentia cujete L. (Bignoniaceae) / Phytotoxicity of the organic phase and major compound obtained from the fruit pulp of Crescentia cujete L. (Bignoniaceae)

Avaliou-se a itotoxicidade do extrato etanólico (CETOH), da fase orgânica (CEA) e do composto majoritário, o ácido (E)-cinâmico (AC), obtidos da polpa dos frutos da espécie popularmente conhecida como cujuba, cuieira e/ou cabaça (Crescentia cujete L.) sobre a inibição da germinação de sementes, desenvolvimento do hipocótilo e radícula das plantas invasoras Senna obtusifolia (L.) Irwin & Barneby (mata-pasto) e Mimosa pudica Mill. (malícia). A fase orgânica na concentração de 0,5% inibiu em 100% a germinação das sementes das duas plantas invasoras. O AC que foi obtido da fase orgânica inibiu a germinação das sementes de S. obtusifolia em 95% e de M. pudica em 99% na concentração de 0,1%, com concentração (%) tóxica para inibição de 50% (CI50) da germinação das sementes iguais a 0,063 e 0,037%, respectivamente; e nos bioensaios de crescimento de plântula, o AC foi mais eiciente sobre a radícula da planta S. obtusifolia (com CI50 igual a 0,009%) e para a planta M. pudica os valores de CI50 foram de 0,097% e 0,117% para a radícula e hipocótilo, respectivamente. Essa pesquisa reforça o potencial itotóxico do ácido (E)-cinâmico, veriicado inicialmente na fase orgânica em acetato de etila (CEA) rica nesse fenilpropanoide.

The phytotoxity of ethanol extracts, of the organic phase and major compound (cinnamic acid) obtained from the fruit pulp of Crescentia cujete L., were evaluated for their potential to inhibit seed germination, hypocotyl development and radicle development of the invasive weeds Senna obtusifolia (L.) Irwin & Barneby and Mimosa pudica Mill. The organic phase at a concentration of 0.5% inhibited 100% seed germination of both weeds. Cinnamic acid obtained from the organic phase inhibited seed germination by 95% for S. obtusifolia and 99% for M. pudica at a concentration of 0.1%, with concentrations (%) inhibiting 50% (IC50) seed germination equal to 0.063% and 0.037%, respectively. For the seedling growth bioassays, the toxicity of the cinnamic acid was more eicient for the S. obtusifolia radicle (IC50 equal to 0.009%), and for M. pudica the IC50 values were 0.097% and 0.117% for the radicle and hypocotyl, respectively. This research reinforces the phytotoxic potential of cinnamic acid, veriied initially in the organic phase (in ethyl acetate), which is rich in this phenylpropanoid.

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.

Morte súbita em bovinos causada pela ingestão de Pseudocalymma elegans (Bignoniaceae) no município de Rio Bonito, RJ / Sudden death in cattle caused by ingestion of Pseudocalymma elegans (Bignoniaceae) in the county of Rio Bonito, Rio de Janeiro

Descreve-se a intoxicação natural por Pseudocalymma elegans em pelo menos um bovino em Rio Bonito, RJ e a reprodução experimental dessa intoxicação em três bovinos e em 3 coelhos com exemplares dessa planta colhida no local onde ocorreu a morte. Necropsia e histopatologia do bovino naturalmente intoxicado não revelaram alterações significativas. A administração, por via oral, de 1g/kg da brotação da planta causou a morte do bovino dentro de 5h e 30 minutos após o início da administração, já pela administração de 0,5 g/kg, a morte do animal ocorreu após 76 horas e 36 minutos. A dose de 0,25g/kg foi capaz de causar sintomas, mas não levou a morte. A sintomatologia caracterizou-se por arritmia cardíaca, taquicardia, aumento da freqüência respiratória, relutância em se mover, pulso venoso positivo, jugulares e grandes vasos ingurgitados, queda ao solo e movimentos de pedalagem, seguindo-se o óbito. À necropsia foram verificadas alterações compatíveis com às observadas na insuficiência cardíaca aguda, e o exame histopatológico revelou a lesão renal típica (degeneração hidrópica em túbulos contornados distais) de intoxicação por plantas que causam "morte súbita". Nos coelhos, a evolução variou entre menos de um minuto a dois minutos. O exame histopatológico do rim de dois coelhos também revelou a lesão microscópica característica. Essa planta ainda não havia sido mapeada nessa área do Estado do Rio de Janeiro. Conclui-se que a planta pode ser mais tóxica do que anteriormente descrito.

Natural poisoning by Pseudocalymma elegans, a plant that causes "sudden death" and only occurs in the State of Rio de Janeiro, is described in a cow. This condition was experimentally reproduced in three calves and three rabbits with the plant collected in the area where the deaths had occurred. Postmortem and histopathological examinations of the natural case in the cow did not reveal significant alterations. Oral administration of 1g/kg of the sprouts of P. elegans caused death of the calf 5 hours and 30 minutes after beginning of the administration. The dose of 0.5 g/kg caused death of another calf with onset of symptoms after 3 hours and 24 minutes and a course of 73 hours and 12 minutes. Animals that ingest borderline doses may show a longer course with a characteristic clinical picture of heart impairment. The dose of 0.25g/kg did not cause death, but only clinical signs. Heart palpitation and arrhythmia, increase of breathing frequency, reluctance in moving, positive venous pulse, ingurgitated jugular veins, falling down and peddling movements shortly before death, were observed. At postmortem examination the lesions were those of acute heart insufficiency, and histopathological examination revealed the typical kidney lesion (hydropic-vacular degeneration in the distal convoluted tubules) seen in poisoning by plants that cause "sudden death". In the experimentally poisoned rabbits the clinical course was less than 1-2 minutes. In the kidney of two rabbits there was also the characteristic microscopic lesion. The presence of the plant in the county of Rio Bonito had not been known by the veterinarians. It is concluded that the plant could be more toxic than described before.

Variação da toxidez de Arrabidaea bilabiata (Bignoniaceae) em coelhos / Variation of the toxicity of Arrabidaea bilabiata (Bignoniaceae) in rabbits

A brotação e as folhas maduras dessecadas e trituradas de Arrabidaea bilabiata, um cipó ou arbusto escandente da família Bignoniaceae, foram administradas em suspensão aquosa por via intragástrica a 15 coelhos adultos nas doses que variaram de 0,25-6,0g/kg. Nos experimentos com a brotação coletada em outubro (fim da época de seca), a menor dose que causou a morte dos coelhos foi de 0,5g/kg e em maio (fim da época de cheia), a menor dose que causou a morte foi de 1,0g/kg. Já com as folhas maduras coletadas em outubro a menor dose que causou a morte dos coelhos foi de 4,0g/kg e em maio, a menor dose que causou a morte foi de 6,0g/kg. A evolução em todos os casos letais foi superaguda. Clinicamente os coelhos de súbito debatiam-se com força na gaiola, caiam em decúbito lateral ou esternal, faziam movimentos de pedalagem, apresentavam acentuada dispnéia e morriam. A necropsia não foram observadas alterações significativas e ao exame histopatológico as lesões mais importantes caracterizaram-se, nos rins, por degeneração hidrópico-vacuolar das células epiteliais dos túbulos contornados distais, no fígado por vacuolização difusa do citoplasma e necrose de hepatócitos, predominantemente centro-lobular e paracentral e presença de esférulas eosinofílicas nos sinusóides hepáticos, no coração, por grupos de fibras cardíacas com eosinofilia aumentada, além de congestão nos rins, fígado, coração e pulmão. Neste estudo ficou estabelecido que a toxidez de A. bilabiata varia de acordo com a época do ano e o estado de maturação, pois essa planta foi mais tóxica em outubro e quando em brotação, confirmando, assim, os dados obtidos previamente em bovinos e búfalos.

The dried and powdered mature leaves and sprouts of Arrabidaea bilabiata (fam. Bignoniaceae), a liana or scandent shrub, were administered by stomach tube to 15 rabbits at doses of 0.25-6.0g/kg. The lowest dose of the sprouts collected in October (End of the dry season) causing death was 0.5g/kg, whilst the lowest lethal dose of sprouts collected in May (End of the rainy season) was 1.0g/kg. With the mature leaves collected in October the lowest lethal dose was of 4.0g/kg, and the lowest lethal dose of the mature leaves collected in May was 6.0g/kg. The clinical course of the poisoning was peracute. The rabbits all of a sudden fell down with struggling movements, difficult and spaced breathing, and died. At necropsy, significant alterations were not observed and histopatological examination showed, as the more important changes, vacuolar hydropic degeneration of epithelial cells of the distal convoluted renal tubules, diffuse vacuolation of the cytoplasm and necrosis of hepatocytes, presence of eosinophilic sphaerules in the sinusoids, groups of heart muscle fibers with increased eosinophilia, besides congestion in the kidneys, liver, heart and lungs. It was concluded that the toxicity of A. bilabiata varies according to the season of the year and the growth stage of the plant. The plant was most toxic in October and the sprouts were more toxic than the mature leaves, confirming the data previously obtained in experiments with cattle and buffalos.