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1.
Biochem Pharmacol ; 181: 114119, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32589997

RESUMO

Epilepsy accounts for one of the most serious neurological disorders, and its treatment remains a challenge, due to high cost and harmful side effects. Bioactive molecules extracted from arthropod venoms are considered a promising therapy since these compounds are known for their highly selective and potent profiles. The purpose of this study was to identify and characterize the potential antiseizure effect of the peptide Ppnp7, extracted from the venom of the social wasp Polybia paulista, and also the effect of the bioinspired peptide, named Neuropolybin, in the same parameters. Additionally, we also evaluated the electroencephalographic (EEG) profile in the PTZ-induced acute seizures in animals treated with Neuropolybin, and potential adverse effects of both peptides in general spontaneous activity (Open Field analysis). Interestingly, Ppnp7 and Neuropolybin showed a noteworthy antiseizure effect in rats and mice, respectively. Curves of protection against the maximum seizure were obtained for both peptides, and EEG records demonstrated that Neuropolybin protected 80% of animals from tonic-clonic seizures when applied with a dose of 3 nmol (an approximate Ppnp7 ED50 found in rats). Neuropolybin and Ppnp7 did not cause changes in the general spontaneous activity of the animals in any of the doses evaluated. Therefore, this study demonstrated how compounds isolated from wasps' venom may be essential resources in the search for new drugs, and can also be considered valuable therapeutic and biotechnological tools for the study and future treatment of epileptic disorders.


Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/prevenção & controle , Peptídeos/farmacologia , Convulsões/prevenção & controle , Animais , Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Feminino , Masculino , Camundongos , Pentilenotetrazol , Peptídeos/química , Peptídeos/uso terapêutico , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Venenos de Vespas/química , Venenos de Vespas/metabolismo
2.
PLoS One ; 11(3): e0149729, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26930596

RESUMO

Mycobacterium abscessus subsp. massiliense, a rapidly growing mycobacteria (RGM) that is becoming increasingly important among human infectious diseases, is virulent and pathogenic and presents intrinsic resistance to several antimicrobial drugs that might hamper their elimination. Therefore, the identification of new drugs to improve the current treatment or lower the risk of inducing resistance is urgently needed. Wasp venom primarily comprises peptides that are responsible for most of the biological activities in this poison. Here, a novel peptide Polydim-I, from Polybia dimorpha Neotropical wasp, was explored as an antimycobacterial agent. Polydim-I provoked cell wall disruption and exhibited non-cytotoxicity towards mammalian cells. Polydim-I treatment of macrophages infected with different M. abscessus subsp. massiliense strains reduced 40 to 50% of the bacterial load. Additionally, the Polydim-I treatment of highly susceptible mice intravenously infected with M. abscessus subsp. massiliense induced 0.8 to 1 log reduction of the bacterial load in the lungs, spleen, and liver. In conclusion, this is the first study to show the therapeutic potential of a peptide derived from wasp venom in treating mycobacteria infections. Polydim-I acts on the M. abscessus subsp. massiliense cell wall and reduce 40-90% of the bacterial load both in vitro and in vivo. The presented results encourage further studies on the use of Polydim-I as one of the components for M. abscessus subsp. massiliense treatment.


Assuntos
Antibacterianos/farmacologia , Infecções por Mycobacterium/tratamento farmacológico , Mycobacterium/efeitos dos fármacos , Peptídeos/farmacologia , Vespas/metabolismo , Sequência de Aminoácidos , Animais , Antibacterianos/química , Linhagem Celular , Células Cultivadas , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Proteínas de Insetos/química , Proteínas de Insetos/farmacologia , Interferon gama/deficiência , Interferon gama/genética , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Camundongos Endogâmicos BALB C , Camundongos Knockout , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Mycobacterium/fisiologia , Mycobacterium/ultraestrutura , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/microbiologia , Peptídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Venenos de Vespas/metabolismo
3.
Toxicon ; 113: 41-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26854369

RESUMO

Envenomation by wasp stings is a public health preoccupation, and signals after stings have variable effects depending on the number of attacks and individual sensitivities. Even with the high rate of wasp sting cases, the study of phatophysiological effects of the envenomation is still very incipient. In this context, early and accurate assessment of this prognostic can aid in the reduction of the symptomatology and complete remission of the later symptoms. Then, the present study evaluated the toxicological effects caused by envenomation produced by Synoeca surinama, a wasp easily found in Neotropical regions. In vivo tests comprised the evaluation of LD50 (OECD 423), nociception, edema, myotoxic lesion and hemorrhage induction, in vitro tests were realized to evaluate hemolysis, contractile and coagulation alteration. The envenomation effects observed were dose- and time-dependent; the LD50 observed for S. surinama was 178 µg/kg, approximately 17 times more lethal than that of the honeybee. Moreover, a potent algesic and oedema effect, and weak hemorrhagic signal were observed after injection of the venom wasp. Assays in vitro showed that this venom is able to prolong the clotting time of plasma and to increase creatine kinase levels. Our results demonstrated that this venom induced serious local and systemic effects in mammals and, so, to avoid permanent damage to the patient, health professionals should carefully investigate each accident. Moreover, due to its high occurrence in Neotropical regions, ecological management, particularly in areas with free access of children and elderly, should be performed.


Assuntos
Venenos de Vespas/toxicidade , Vespas/fisiologia , Animais , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Cobaias , Dose Letal Mediana , Camundongos , Músculo Liso/efeitos dos fármacos , Medição da Dor , Ratos , Venenos de Vespas/administração & dosagem
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