Isohemigossypolone: Antiophidic properties of a naphthoquinone isolated from Pachira aquatica Aubl.

We investigated the antiophidic properties of isohemigossypolone (ISO), a naphthoquinone isolated from the outer bark of the Pachira aquatic Aubl. The inhibition of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic activities induced by Bothrops pauloensis venom (Pb) was investigated. For this, we use samples resulting from the incubation of Pb with ISO in different concentrations (1:1, 1:5 and 1:10 w/w), we also evaluated the condition of treatment using ISO after 15 min of venom inoculation. The activities of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic induced by the B. pauloensis venom were significantly inhibited when the ISO was pre-incubated with the crude venom. For in vivo neutralization tests, the results were observed even when the ISO was applied after 15 min of inoculation of the venom or metalloprotease (BthMP). Also, to identify the inhibition mechanism, we performed in silico assays, across simulations of molecular coupling and molecular dynamics, it was possible to identify the modes of interaction between ISO and bothropic toxins BmooMPα-I, Jararacussin-I and BNSP-7. The present study shows that naphthoquinone isohemigossypolone isolated from the P. aquatica plant inhibited part of the local and systemic damage caused by venom proteins, demonstrating the pharmacological potential of this compound in neutralizing the harmful effects caused by snakebites.

Antiophidic activity of the secondary metabolite lupeol isolated from Zanthoxylum monogynum.

Previous studies have demonstrated the potential antiophidic activity of Zanthoxylum monogynum A.St.-Hil. a tree from the Rutaceae family native to South America. In this present contribution, we demonstrate the activity of the metabolite lupeol, a triterpenoid isolated from the stem bark of Z. monogynum against the harmful effects of the Bothrops alternatus venom. We investigated the antiophidic properties of lupeol, for this purpose, and use crude venom (Pb) incubated with lupeol in different concentrations, testing in vitro experiments and inoculated in mice for inhibitory evaluations in vivo. Besides, we tried to elucidate through the molecular dynamics the mechanism of action of lupeol with the bothropic thrombin-like toxin Jararacussin-I; the acidic phospholipase A2 toxin BthA-I from Bothrops jararacussu and the metalloproteinase toxin BmooMP-I from Bothrops moojeni. In our results, we demonstrated the potential inhibitory effect upon coagulant, phospholipasic and myotoxic activities of the bothropic venom, previously incubated with lupeol. We found that lupeol triterpenoid was able to partially inhibit local and systemic damage caused by snake venom toxins. Our in silico results demonstrate that lupeol is capable of interacting and altering the activity of the thrombin-like toxin Jararacussin-I, and capable of interacting with the BthA-I acidic PLA2, both toxins present in Bothrops snakes venom, thus demonstrating the pharmacological potential of this compound for the treatment of bothropic accidents.

Clinical-epidemiologic aspects of ophidian accidents occurred in Triângulo Mineiro region, Minas Gerais State, Brazil: retrospective case series / Aspectos clínico-epidemiológicos dos acidentes ofídicos ocorridos na região do Triângulo Mineiro, Minas Gerais, Brasil: estudo retrospectivo

Ophidian accidents constitute a serious problem of public health in the tropical countries. In Central and South America, most of the accidents are caused by Bothrops (90.5%), followed by the Crotalus (7.7%), Lachesis (1.4%) and Micrurus (0.4%) genus. The aim of this work was to evaluate clinical-epidemiological aspects of ophidian accidents reported and treated at the Clinical Hospital at Federal University of Uberlândia, in the central region of Brazil. In this study, 641 medical records from January 1999 to December 2013 were analyzed. The results showed that the accidents were more common in the afternoon, from October to April. The major bite occurrence frequency was attributed to the Bothrops (54.76%), followed by Crotalus (30.58%) and Micrurus (1.40%) snakes. Most of the victims were males (80.34%). The main anatomical regions bitten were the lower and upper limbs, 65.67% and 30.58%, respectively. Approximately 80% of the victims were treated in the first 6 hours after the accident.

Os acidentes ofídicos constituem um sério problema de saúde pública em países tropicais. Nas Américas Central e do Sul, a maioria dos acidentes são causados pelo gênero Bothrops (90,5%), seguido por Crotalus (7,7%), Lachesis (1,4%) e Micrurus (0,4%). O objetivo deste trabalho foi avaliar os aspectos clínico-epidemiológicos dos acidentes ofídicos registrados e tratados no Hospital de Clínicas da Universidade Federal de Uberlândia, na região central do Brasil. Neste estudo, foram analisados 641 prontuários médicos de janeiro de 1999 a dezembro de 2013. Os resultados mostraram que os acidentes ofídicos foram mais comuns durante o período da tarde, de outubro a abril. A maior frequência de ocorrência das picadas foi atribuída às serpentes do gênero Bothrops (54,76%), seguido por Crotalus (30,58%) e Micrurus (1,40%). A maioria das vítimas foi do sexo masculino (80.34%). As principais regiões anatômicas acometidas foram os membros inferiores e superiores, 65,67% e 30,58%, respectivamente. Aproximadamente 80% das vítimas foram tratadas nas primeiras 6 horas após o acidente.

Predição da neutralização do efeito coagulante da peçonha de Bothrops pauloensis pelo extrato aquoso de Hedychium coronarium (Zingerberaceae) através de modelos de regressão / Prediction of neutralization of clotting effect of venom bothrops pauloensis by aqueous extract of hedychium coronarium (zingeberaceae) through of regression models

Envenenamentos com serpentes do gênero Bothrops podem causar sequelas no local da picada, que não são revertidas mesmo após o tratamento com soro antiofídico. A incubação do extrato aquoso de Hedychium coronarium (Zingeberaceae) com a peçonha da serpente Bothrops pauloensis em diferentes concentrações foi capaz de inibir a atividade coagulante. No presente trabalho ajustou-se um modelo de regressão entre níveis de concentração de extrato e tempo de coagulação (segundos). O modelo ajustado conseguiu captar cerca 96 % da variação total do tempo de coagulação.

Envenomations with snakes Bothrops genus can cause dependency at the sting site, which are not reversed even after treatment with snake antivenoms. Incubation of the aqueous extract of Hedychium coronarium (Zingeberaceae) with snake venom Bothrops pauloensis in different concentrations was able to inhibit some enzymatic activities. This work has set a model of regression between concentrations of extract and clotting time (seconds). The adjusted model has captured about 96% of the total variation of clotting time

Insights of local tissue damage and regeneration induced by BnSP-7, a myotoxin isolated from Bothrops (neuwiedi) pauloensis snake venom.

Envenomations caused by Bothrops snake venoms are characterized by prominent local tissue damage due to myonecrosis, hemorrhage, edema and acute muscle damage which is widely correlated with phospholipases A2 (PLA2). In the present study, the progression of local tissue damage and inflammation induced by BnSP-7, a myotoxin isolated from Bothrops (neuwiedi) pauloensis snake venom, was evaluated. Local tissue damages characterized by edema, necrosis and inflammation were evaluated until 24 h after inoculation of BnSP-7. The regeneration of myofibers, analyzed by light microscopy, was observed from 72 h to 2 weeks post-inoculation of toxin. MMP-2 was expressed in gastrocnemius muscle at all time points tested, while the expression of MMP-9 increased expressively at the same time interval of regenerating muscle, suggesting the involvement of MMP-9 in the regeneration process. The production of pro-inflammatory cytokines was also increased, whereas IL-1 beta showed the highest level. Modification of BnSP-7 with BPB decreased the release of IL-8, IL-6 and IL-1 beta when compared to native BnSP-7. These data suggest that BnSP-7 acts as pro-inflammatory incentives (mediators), inducing MMP and cytokine production from the inflammatory and satellite cells, and thus it may play an important role in inflammatory process and, consequently, in the evolution of local tissue damage and regeneration.