Effects of pyriproxyfen on zebrafish brain mitochondria and acetylcholinesterase.

Pyriproxyfen is an insecticide used worldwide that acts as a biomimetic of juvenile hormone. This study investigated metabolic and synaptic impairments triggered by pyriproxyfen using zebrafish acetylcholinesterase (zbAChE) and mitochondria as markers. A brain zbAChE assay was performed in vitro and in vivo covering a range of pyriproxyfen concentrations (0.001-10 µmol/L) to assess inhibition kinetics. Docking simulations were performed to characterize inhibitory interactions. Zebrafish male adults were acutely exposed to 0.001, 0.01 and 0.1 µg/mL pyriproxyfen for 16 h. Mitochondrial respiration of brain tissues was assessed. ROS generation was estimated using H2DCF-DA and MitoSOX. Calcium transport was monitored by Calcium Green™ 5 N. NO synthesis activity was estimated using DAF-FM-DA. Brain acetylcholinesterase showed an in vivo IC20 of 0.30 µmol/L pyriproxyfen, and an IC50 of 92.5 µmol/L. The inhibitory effect on zbAChE activity was competitive-like. Respiratory control of Complex I/II decreased significantly after insecticide exposure. The MitoSOX test showed that O2- generation had a pyriproxyfen dose-dependent effect. Brain tissue lost 50% of Ca2+ uptake capacity at 0.1 µg/mL pyriproxyfen. Ca2+ release showed a clear mitochondrial impairment at lower pyriproxyfen exposures. Thus, Ca2+ transport imbalance caused by pyriproxyfen may be a novel deleterious mechanism of action. Overall, the results showed that pyriproxyfen can compromise multiple and interconnected pathways: (1) zbAChE impairment and (2) the functioning of the electron transport chain, ROS generation and calcium homeostasis in zebrafish brain mitochondria. Considering the many similarities between zebrafish and human, more caution is needed when pyriproxyfen is used in both urban and agricultural pest control.

Poly-ε-Caprolactone Microsphere Polymers Containing Usnic Acid: Acute Toxicity and Anti-Inflammatory Activity.

Usnic acid (UA) has been studied by its pharmacological properties; however, it presents moderate toxicity, low solubility, and absorption by biological membranes. The aim of this study was to develop poly-ε-caprolactone microsphere polymers containing UA (UA-micro) and evaluate their acute toxicity and anti-inflammatory activity. The microspheres were prepared by multiple emulsion technique (water/oil/water) and characterized by the encapsulation efficiency, particle size, polydispersity index, and zeta potential. The acute toxicity of UA and UA-micro (25-50 mg/kg; p.o.) was evaluated in mice. The anti-inflammatory activity of UA and UA-micro was evaluated by subcutaneous air pouch and carrageenan-induced paw edema in rat, with measurement of inflammatory cytokines and MPO levels. The UA presented encapsulation efficiency of 97.72%, particle size of 13.54 micrometers, polydispersity index of 2.36, and zeta potential of 44.5 ± 2.95 mV. The UA-micro presented lower acute toxicity (LD50 value up to 2000 mg/kg; p.o.) when compared to UA. UA-micro and UA (25 mg/kg) significantly reduced paw volume and decreased MPO levels, whereas only UA-micro (50 mg/kg) reduced significantly IL-1ß, TNF-α, and NO levels in inflammatory exudate. These results suggest that controlled release systems, as microspheres, can be a promising alternative to reduce the toxicity of UA, making it a viable compound for inflammation therapy.

Aspectos botânicos e clínicos das intoxicações por plantas das Famílias Araceae, Euphorbiaceae e Solanaceae no Estado de Pernambuco / Bothanical and clinical aspectos of intoxications caused by plants of the Araceae, Euphorbiaceae and Solanaceae family in the state of Pernambuco

Trata-se de um estudo investigativo sobre os aspectos botânicos e clínicos das intoxicações humanas provocadas por espécies das famílias Araceae, Euphorbiaceae e Solanaceae. É um estudo transversal, descritivo, com abordagem quantitativa, aprovado pelo Comitê de Ética do Hospital da Restauração. Os dados referentes ao período de 1992 a 2009 foram coletados no Centro de Assistência Toxicológica de Pernambuco (CEATOX). Dos 214 prontuários analisados, 140 tiveram diagnóstico de intoxicação por espécies das famílias Araceae (55%; n=77); Euphorbiaceae (36,43%; n=51) e Solanaceae (8,57%; n=12). A maioria das Araceae foi representada por Dieffenbachia amoena Bull (50%); Euphorbiaceae por Manihot esculenta Crantz (11,42%) e Solanaceae por Brugmansia suaveolens (Willd.) Bercht. & J. Presl. (5,71%), utilizadas como ornamental, alimentícia, medicinal, em brincadeiras infantis e suicídio. Em consequência da ingestão de partes dessas plantas os sintomas apresentados foram: edema (língua, lábio), náusea, diarreia, rubor facial, midríase, alucinações e dores abdominais. O tratamento constou de observação clínica (45,31%) e tratamento sintomático (40,18%). A gravidade das intoxicações foi classificada como aguda moderada em 79,69% dos pacientes.(AU)

This is an investigative study about the clinical and botanical aspects of human poisoning caused by plants of the species Araceae, Euphorbiaceae and Solanaceae. It is a cross-sectional descriptive study with a quantitative approach, approved by the Restoration Hospital Ethics Committee. Data was collected at the Toxicological Assistance Centre of Pernambuco (CEATOX) comprising the period of 1992 to 2009. 214 records were analyzed, 140 had an intoxication diagnostic from the families: Araceae (55%, n = 77); Euphorbiaceae (36,43%; n = 51) and solanaceae (8,57%; n = 12). Aracea was majorly represented by Dieffenbachia Amoena Bull (50%); Euphorbiaceae by Manihot esculenta Crantz (11,42%) and Solanaceae by Brugmansia suaveolens (Willd.) Bercht. & J. Presl. (5, 71%) that were used as ornamental plants, food, medicine, in children's play and suicide attempts. As a result of ingestion of parts of the plant the symptoms were edema (tongue, lips), nausea, diarrhea, facial flushing, mydriasis, hallucinations and abdominal pain. Treatment consisted of clinical observation (45,31%) and symptomatic treatment (40,18%). The severity of the intoxications was classified as 'moderate acute' in 79,69% of patients.(AU)

Indican from Añil (Indigofera suffruticosa Miller) as an herbal protective agent to the liver.

OBJECTIVE: To investigate the antitumor activity of mice bearing sarcoma 180 cell lines treated with indican of Indigofera suffruticosa and the histological and morphometric analysis on the liver of those animals. STUDY DESIGN: The mice were divided into 3 groups: Group 1 (G1) and Group 3 (G3) bearing sarcoma 180, and Group 2 (G2) without sarcoma 180. G1 and G2 (controls) were administered saline; G3 was treated with indican (25 mg/kg, i.p.). RESULTS: The purified indican after subchronic treatment did not significantly reduce the mean volume of sarcoma 180 when compared with control G1. HistopathologicaI and morphometric analysis of the liver of G2 and G3 did not show degenerated areas, compared to. G1 which showed pronounced destruction of the liver architectures. CONCLUSION: The results showed that the inhibition of solid tumor growth was not significant; however, the indican from leaves of I. suffruticosa preserved the liver architectures, suggesting its use as an alternative protective agent of the liver tissue.

Pharmacokinetics of the venom of Bothrops erythromelas labeled with 131I in mice.

Bothrops erythromelas venom (BeV) has been responsible for many snake accidents in Brazil. We investigated the plasmatic pharmacokinetic of BeV labeled with (131)I in the absence and the presence of anti-Bothrops serum (BAS). A higher percentage of BeV plasmatic radioactivity and longer elimination were found in the presence of BAS. Our results showed a redistribution of venom from the tissue to vascular compartment associated with the treatment of envenomed mice with anti-venom 15 min after venom injection.

Avaliação da atividade antiinflamatória e analgésica do extrato bruto hidroalcoólico do zoantídeo Palythoa caribaeorum (Duchassaing & Michelotti, 1860) / Evaluation of the anti-inflammatory and analgesic activity of the crude hydroalcoholic extract of the zoanthid Palythoa caribaeorum (Duchassaing & Michelotti, 1860)

O presente trabalho representa a primeira análise das atividades analgésica e antiinflamatória do extrato bruto hidroalcoólico do zoantídeo Palythoa caribaeorum. Foram realizados os testes de Writhing induzido por ácido acético (1 por cento, 10 mL.kg-1 i.p.) e da chapa quente em camundongos para avaliar o efeito analgésico; e o teste de edema de pata de rata induzido por carragenina para avaliar a atividade antiinflamatória. As análises evidenciaram atividade analgésica no teste de Writhing no grupo tratado com 200 mg.kg-1 v.o. de extrato, com uma inibição de 47,22 por cento do número de contorções abdominais ("Writhings"), revelando atividade estatisticamente significativa.

This work represents the first pharmacological analysis on the crude hydroalcoholic extract of Palythoa caribaeorum. The analgesic activity was assayed in acetic acid-induced writhing test and with the hot-plate test with mice; while the anti-inflammatory activity was evaluated in carrageenan-induced hind paw edema in the rat. The analysis suggested an analgesic activity in the Writhing test on the group treated with the crude extract (200 mg.kg-1 v.o.) with an abdominal contortionÆs inhibition of 47,22 percent.