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.

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.

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.

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.