Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)

Detalhes bibliográficos
Autor(a) principal: Bruna Luiza Emerich Magalhães
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/34532
Resumo: The venom of the “armed” spider Phoneutria nigriventer has several biologically active components including peptides, proteins, amino acids, salts etc. The symptoms resulting from this animal’s bite comprise local pain, arousal, salivation, lacrimation, priapism, seizures and spastic and flaccid paralysis of the anterior and posterior limbs. The toxin PnTx4(6-1), isolated from the PhTx4 fraction of these venom, is a single chain polypeptide composed of 48 amino acid residues, with a mass of 5244.6 Da. This polypeptide was initially described as a neurotoxin insecticide. PnTx4(6-1) appears to bind to site 3 of sodium channels in nerve cord synaptosomes of cockroach (Periplaneta americana) and slow down inactivation of sodium current in isolated axon of insect, without affecting sodium channels of skeletal muscle (rSKM1) and brain (rBIIA), both of rats. This result corroborated previous assays in which the intracerebral injection of the toxin (up to 30μg) in mice caused no apparent toxicity. The present study evaluated the antinociceptive effect of the PnTx4(6-1) in three experimental pain models, using the test paw withdrawal, subjected to compression (Randall & Selitto, 1957). The hyperalgesia in inflammatory pain model was caused by intraplantar injection of 250 μg of carrageenan. When administered in the same place, after an interval of two hours and thirty minutes, PnTx4(6-1) (5 μg) was able to restore the nociceptive threshold of the animals. The hyperalgesia in nociceptive pain model, was evoked by intraplantar injection of 2 μg of prostaglandin E2 (PGE2). The central administration of PnTx4(6-1) by intrathecal injection caused a dose-dependent antinociceptive effect against the hyperalgesia induced by PGE2. Briefly, a dose of 100 pmoles was able to raise the nociceptive threshold of the paw of rats, and the doses of 200 and 400 pmoles totally reversed the hyperalgesic effect evoked by PGE2, with duration of 30 minutes. The measurements in the contralateral paw revealed that PnTx4(6-1), when centrally administered, does not alter the nociceptive threshold of the paw untreated. Concerning to the neuropathic pain model the toxin (100 pmoles) reversed, lasting ten minutes, the hyperalgesia evoked by constriction of the sciatic nerve. This research with PnTx4(6-1) indicates a strong therapeutic potential to this molecule as a possible model to new analgesic.
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spelling Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)Toxina de aranhaPnTx4(6-1)NocicepçãoPhoneutria nigriventerNociceptividadeVenenos de AranhaPhoneutria nigriventerThe venom of the “armed” spider Phoneutria nigriventer has several biologically active components including peptides, proteins, amino acids, salts etc. The symptoms resulting from this animal’s bite comprise local pain, arousal, salivation, lacrimation, priapism, seizures and spastic and flaccid paralysis of the anterior and posterior limbs. The toxin PnTx4(6-1), isolated from the PhTx4 fraction of these venom, is a single chain polypeptide composed of 48 amino acid residues, with a mass of 5244.6 Da. This polypeptide was initially described as a neurotoxin insecticide. PnTx4(6-1) appears to bind to site 3 of sodium channels in nerve cord synaptosomes of cockroach (Periplaneta americana) and slow down inactivation of sodium current in isolated axon of insect, without affecting sodium channels of skeletal muscle (rSKM1) and brain (rBIIA), both of rats. This result corroborated previous assays in which the intracerebral injection of the toxin (up to 30μg) in mice caused no apparent toxicity. The present study evaluated the antinociceptive effect of the PnTx4(6-1) in three experimental pain models, using the test paw withdrawal, subjected to compression (Randall & Selitto, 1957). The hyperalgesia in inflammatory pain model was caused by intraplantar injection of 250 μg of carrageenan. When administered in the same place, after an interval of two hours and thirty minutes, PnTx4(6-1) (5 μg) was able to restore the nociceptive threshold of the animals. The hyperalgesia in nociceptive pain model, was evoked by intraplantar injection of 2 μg of prostaglandin E2 (PGE2). The central administration of PnTx4(6-1) by intrathecal injection caused a dose-dependent antinociceptive effect against the hyperalgesia induced by PGE2. Briefly, a dose of 100 pmoles was able to raise the nociceptive threshold of the paw of rats, and the doses of 200 and 400 pmoles totally reversed the hyperalgesic effect evoked by PGE2, with duration of 30 minutes. The measurements in the contralateral paw revealed that PnTx4(6-1), when centrally administered, does not alter the nociceptive threshold of the paw untreated. Concerning to the neuropathic pain model the toxin (100 pmoles) reversed, lasting ten minutes, the hyperalgesia evoked by constriction of the sciatic nerve. This research with PnTx4(6-1) indicates a strong therapeutic potential to this molecule as a possible model to new analgesic.A peçonha da aranha Phoneutria nigriventer, conhecida como “aranha armadeira”, possui diversos componentes biologicamente ativos. Entre os sintomas decorrentes da picada desse animal destacam-se dor local, excitação, salivação, lacrimejamento, priapismo, convulsão e paralisia flácida e espástica dos membros anteriores e posteriores. A toxina PnTx4(6-1) foi isolada da fração PhTx4 deste veneno, sendo um polipeptídeo de cadeia única composto por 48 resíduos de aminoácidos, cuja massa é de 5244,6 Da. PnTx4(6-1) foi inicialmente descrita como uma neurotoxina inseticida, que liga-se ao sítio 3 de canais para sódio em sinaptossomas de barata (Periplaneta americana). Entretanto, canais para sódio de músculo esquelético (rSKM1) e cérebro (rBIIA), ambos de ratos, não foram alvos da toxina PnTx4(6-1). Estes resultados corroboraram resultados anteriores em que a injeção intracerebral da toxina purificada (15 e 30 μg), em camundongos, não provocou toxicidade aparente. O presente estudo avaliou o efeito antinociceptivo da toxina PnTx4(6-1) frente a hiperalgesia evocada por carragenina, prostaglandina E2 e por constrição do nervo ciático. A atividade antihiperalgésica foi avaliada pelo teste de retirada da pata do rato submetida à compressão, descrito originalmente por Randall & Selitto, em 1957. A hiperalgesia no modelo de dor inflamatória foi causada pela injeção intraplantar de 250 μg de carragenina. Quando administrada no mesmo local, após intervalo de duas horas e trinta minutos, a toxina PnTx4(6-1) (5 μg) foi capaz de restaurar o limiar nociceptivo da pata dos animais. A hiperalgesia, no modelo de dor nociceptiva, foi evocada pela injeção intraplantar de 2 μg de prostaglandina E2. A administração central da toxina, por injeção intratecal, causou um efeito antinociceptivo dose-dependente. As doses de 200 e 400 pmoles reverteram totalmente o efeito hiperalgésico evocado por prostaglandina E2, tendo duração de 20 minutos. Medidas na pata contralateral revelaram que PnTx4(6-1), quando administrada pela via intratecal, não altera o limiar nociceptivo da pata não tratada. Com relação ao modelo de dor neuropática a toxina na dose de 100 pmoles reverteu, com duração de dez minutos, a hiperalgesia evocada por constrição do nervo ciático. A investigação das propriedades biológicas das toxinas animais e a perspectiva de sua utilização para o alívio da dor demonstram forte potencial terapêutico.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPESP - Fundação de Amparo à Pesquisa do Estado de São PauloUniversidade Federal de Minas GeraisBrasilICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIAPrograma de Pós-Graduação em Bioquímica e ImunologiaUFMGMaria Elena de Lima Perez Garciahttp://lattes.cnpq.br/5642915270924367Igor Dimitri Gama DuarteJanetti Nogueira de FrancischiAlessandra Cristine de Souza MatavelBruna Luiza Emerich Magalhães2020-12-17T11:45:52Z2020-12-17T11:45:52Z2013-02-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/34532porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2020-12-17T11:45:52Zoai:repositorio.ufmg.br:1843/34532Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2020-12-17T11:45:52Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
title Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
spellingShingle Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
Bruna Luiza Emerich Magalhães
Toxina de aranha
PnTx4(6-1)
Nocicepção
Phoneutria nigriventer
Nociceptividade
Venenos de Aranha
Phoneutria nigriventer
title_short Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
title_full Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
title_fullStr Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
title_full_unstemmed Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
title_sort Efeito antinociceptivo da toxina PnTx4(6-1), isolada do veneno da aranha Phoneutria nigriventer (Keyserling, 1891)
author Bruna Luiza Emerich Magalhães
author_facet Bruna Luiza Emerich Magalhães
author_role author
dc.contributor.none.fl_str_mv Maria Elena de Lima Perez Garcia
http://lattes.cnpq.br/5642915270924367
Igor Dimitri Gama Duarte
Janetti Nogueira de Francischi
Alessandra Cristine de Souza Matavel
dc.contributor.author.fl_str_mv Bruna Luiza Emerich Magalhães
dc.subject.por.fl_str_mv Toxina de aranha
PnTx4(6-1)
Nocicepção
Phoneutria nigriventer
Nociceptividade
Venenos de Aranha
Phoneutria nigriventer
topic Toxina de aranha
PnTx4(6-1)
Nocicepção
Phoneutria nigriventer
Nociceptividade
Venenos de Aranha
Phoneutria nigriventer
description The venom of the “armed” spider Phoneutria nigriventer has several biologically active components including peptides, proteins, amino acids, salts etc. The symptoms resulting from this animal’s bite comprise local pain, arousal, salivation, lacrimation, priapism, seizures and spastic and flaccid paralysis of the anterior and posterior limbs. The toxin PnTx4(6-1), isolated from the PhTx4 fraction of these venom, is a single chain polypeptide composed of 48 amino acid residues, with a mass of 5244.6 Da. This polypeptide was initially described as a neurotoxin insecticide. PnTx4(6-1) appears to bind to site 3 of sodium channels in nerve cord synaptosomes of cockroach (Periplaneta americana) and slow down inactivation of sodium current in isolated axon of insect, without affecting sodium channels of skeletal muscle (rSKM1) and brain (rBIIA), both of rats. This result corroborated previous assays in which the intracerebral injection of the toxin (up to 30μg) in mice caused no apparent toxicity. The present study evaluated the antinociceptive effect of the PnTx4(6-1) in three experimental pain models, using the test paw withdrawal, subjected to compression (Randall & Selitto, 1957). The hyperalgesia in inflammatory pain model was caused by intraplantar injection of 250 μg of carrageenan. When administered in the same place, after an interval of two hours and thirty minutes, PnTx4(6-1) (5 μg) was able to restore the nociceptive threshold of the animals. The hyperalgesia in nociceptive pain model, was evoked by intraplantar injection of 2 μg of prostaglandin E2 (PGE2). The central administration of PnTx4(6-1) by intrathecal injection caused a dose-dependent antinociceptive effect against the hyperalgesia induced by PGE2. Briefly, a dose of 100 pmoles was able to raise the nociceptive threshold of the paw of rats, and the doses of 200 and 400 pmoles totally reversed the hyperalgesic effect evoked by PGE2, with duration of 30 minutes. The measurements in the contralateral paw revealed that PnTx4(6-1), when centrally administered, does not alter the nociceptive threshold of the paw untreated. Concerning to the neuropathic pain model the toxin (100 pmoles) reversed, lasting ten minutes, the hyperalgesia evoked by constriction of the sciatic nerve. This research with PnTx4(6-1) indicates a strong therapeutic potential to this molecule as a possible model to new analgesic.
publishDate 2013
dc.date.none.fl_str_mv 2013-02-26
2020-12-17T11:45:52Z
2020-12-17T11:45:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/34532
url http://hdl.handle.net/1843/34532
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
Programa de Pós-Graduação em Bioquímica e Imunologia
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
Programa de Pós-Graduação em Bioquímica e Imunologia
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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