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1.
Toxins (Basel) ; 12(9)2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867207

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative condition that affects the Central Nervous System (CNS). Insect venoms show high molecular variability and selectivity in the CNS of mammals and present potential for the development of new drugs for the treatment of PD. In this study, we isolated and identified a component of the venom of the social wasp Parachartergus fraternus and evaluated its neuroprotective activity in the murine model of PD. For this purpose, the venom was filtered and separated through HPLC; fractions were analyzed through mass spectrometry and the active fraction was identified as a novel peptide, called Fraternine. We performed two behavioral tests to evaluate motor discoordination, as well as an apomorphine-induced rotation test. We also conducted an immunohistochemical assay to assess protection in TH+ neurons in the Substantia Nigra (SN) region. Group treated with 10 µg/animal of Fraternine remained longer in the rotarod compared to the lesioned group. In the apomorphine test, Fraternine decreased the number of rotations between treatments. This dose also inhibited dopaminergic neuronal loss, as indicated by immunohistochemical analysis. This study identified a novel peptide able to prevent the death of dopaminergic neurons of the SN and recover motor deficit in a 6-OHDA-induced murine model of PD.


Assuntos
Comportamento Animal/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Peptídeos/farmacologia , Substância Negra/efeitos dos fármacos , Venenos de Vespas/química , Animais , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Feminino , Masculino , Camundongos , Degeneração Neural , Fármacos Neuroprotetores/isolamento & purificação , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Peptídeos/isolamento & purificação , Teste de Desempenho do Rota-Rod , Substância Negra/metabolismo , Substância Negra/fisiopatologia , Vespas
2.
Pharmacol Ther ; 188: 176-185, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29605457

RESUMO

The complex process of pain control commonly involves the use of systemic analgesics; however, in many cases, a more potent and effective polypharmacological approach is needed to promote clinically significant improvement. Additionally, considering side effects caused by current painkillers, drug discovery is once more turning to nature as a source of more efficient therapeutic alternatives. In this context, arthropod venoms contain a vast array of bioactive substances that have evolved to selectively bind to specific pharmacological targets involved in the pain signaling pathway, playing an important role as pain activators or modulators, the latter serving as promising analgesic agents. The current review explores how the pain pathway works and surveys neuroactive compounds obtained from arthropods' toxins, which function as pain modulators through their interaction with specific ion channels and membrane receptors, emerging as promising candidates for drug design and development.


Assuntos
Analgésicos/farmacologia , Venenos de Artrópodes/farmacologia , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Humanos , Dor/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/fisiologia , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-26257776

RESUMO

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.

4.
Toxicon ; 101: 55-62, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25911957

RESUMO

Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by P. maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 µg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 µg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus.


Assuntos
Mordeduras e Picadas/fisiopatologia , Peixes-Gato/metabolismo , Edema/fisiopatologia , Venenos de Peixe/toxicidade , Inflamação/fisiopatologia , Dor/fisiopatologia , Animais , Brasil , Permeabilidade Capilar/efeitos dos fármacos , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/etiologia , Feminino , Venenos de Peixe/química , Água Doce , Hemorragia/etiologia , Hemorragia/fisiopatologia , Inflamação/etiologia , Isoenzimas/metabolismo , Masculino , Camundongos , Nociceptores/efeitos dos fármacos , Nociceptores/patologia , Dor/etiologia , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Ratos Wistar
5.
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1484613

RESUMO

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimers disease, epilepsy, Parkinsons disease, and pathological anxiety.


Assuntos
Animais , Animais Peçonhentos , Doenças do Sistema Nervoso/terapia , Venenos de Artrópodes/uso terapêutico
6.
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-954768

RESUMO

The impact of neurological disorders in society is growing with alarming estimations for an incidence increase in the next decades. These disorders are generally chronic and can affect individuals early during productive life, imposing real limitations on the performance of their social roles. Patients can have their independence, autonomy, freedom, self-image, and self-confidence affected. In spite of their availability, drugs for the treatment of these disorders are commonly associated with side effects, which can vary in frequency and severity. Currently, no effective cure is known. Nowadays, the biopharmaceutical research community widely recognizes arthropod venoms as a rich source of bioactive compounds, providing a plethora of possibilities for the discovery of new neuroactive compounds, opening up novel and attractive opportunities in this field. Several identified molecules with a neuropharmacological profile can act in the central nervous system on different neuronal targets, rendering them useful tools for the study of neurological disorders. In this context, this review aims to describe the current main compounds extracted from arthropod venoms for the treatment of five major existing neurological disorders: stroke, Alzheimer's disease, epilepsy, Parkinson's disease, and pathological anxiety.(AU)


Assuntos
Animais , Venenos de Artrópodes , Produtos Biológicos , Sistema Nervoso Central , Doenças do Sistema Nervoso
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