Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético

Detalhes bibliográficos
Ano de defesa: 2008
Autor(a) principal: Alves, Renata de Sousa
Orientador(a): Monteiro , Helena Serra Azul
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/3840
Resumo: The venom of Tityus serrulatus has a mixture of toxic and non toxic peptides presenting diverse systemic and local effects. The aim of this work was to investigate the cardiovascular and renal effects promoted by the crude venom of the scorpion Tityus serrulatus and its isolated components such as Tityus serrulatus toxin V (TsTx-V), Gamma Toxin and the newly isolated Natriuretic Peptide. The experiments of isolated perfused rat kidney, isolated mesenteric bed, arterial pressure and in vivo perfusion were performed using male Wistar rats weighing 250-300g. The assays with vas deferens were done using Swiss mice weighing 30-40g. The crude venom presented autonomic nervous system effects showed by the contraction of vas deferens. Adrenergic effects were demonstrated specially with the decrease of renal vascular resistance (RVRVTs = 7.51 ± 0.96 vs RVRPz = 5.51 ± 0.43 mmHg/mL.g-1.min-1*,*p<0.05) and renal perfusion pressure (PPVTs = 150.1 ± 18.40 vs PPPz = 118.1 ± 4.00 mmHg*,*p<0.05) induced by the crude venom after kidneys pre-treatment with prazosin. The venoms isolated components showed kidney addictional effects, where TsTx-V caused diuresis while Gamma Toxin increased perfusion pressure. We could also observe the presence of protein inside the tubules and in glomerular spaces after renal histopathologic evaluation in the groups treated with the isolated components. However, only Gamma Toxin promoted an increase of the mesenteric bed perfusion pressure. The Natriuretic Peptide (0.03 and 0.1µg/mL) increased renal perfusion pressure. In addition, the natriuretic peptide increased cyclic guanosine monophosphate (cGMP) urinary excretion, but reduced electrolytes reabsorption in a dependent-concentration manner. The crude venom and the natriuretic peptide increased the arterial blood pressure, but decreased the hematocrit values, evaluated after in vivo experiments. However, the natriuretic peptide increased urinary flow and heartbeat frequency. In vivo renal function was evaluated by the clearance of inulin. The scorpion crude venom decreased the clearance of inulin, but this parameter was increased after natriuretic peptide treatment. The renal cortex blood flux, estimated by the clearance of p-aminohippurate, was reduced after the crude venom treatment. In conclusion, we demonstrated that Tityus serrulatus venom induced renal hemodynamic effects that were blocked in vitro by prasozin. In vivo experiments showed how the crude venom and its isolated components act increasing arterial blood pressure, heartbeat frequency and altered renal function.
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spelling Alves, Renata de SousaMonteiro , Helena Serra Azul2012-10-01T16:30:01Z2012-10-01T16:30:01Z2008ALVES, R. de S. Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético. 2008. 188 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2008.http://www.repositorio.ufc.br/handle/riufc/3840The venom of Tityus serrulatus has a mixture of toxic and non toxic peptides presenting diverse systemic and local effects. The aim of this work was to investigate the cardiovascular and renal effects promoted by the crude venom of the scorpion Tityus serrulatus and its isolated components such as Tityus serrulatus toxin V (TsTx-V), Gamma Toxin and the newly isolated Natriuretic Peptide. The experiments of isolated perfused rat kidney, isolated mesenteric bed, arterial pressure and in vivo perfusion were performed using male Wistar rats weighing 250-300g. The assays with vas deferens were done using Swiss mice weighing 30-40g. The crude venom presented autonomic nervous system effects showed by the contraction of vas deferens. Adrenergic effects were demonstrated specially with the decrease of renal vascular resistance (RVRVTs = 7.51 ± 0.96 vs RVRPz = 5.51 ± 0.43 mmHg/mL.g-1.min-1*,*p<0.05) and renal perfusion pressure (PPVTs = 150.1 ± 18.40 vs PPPz = 118.1 ± 4.00 mmHg*,*p<0.05) induced by the crude venom after kidneys pre-treatment with prazosin. The venoms isolated components showed kidney addictional effects, where TsTx-V caused diuresis while Gamma Toxin increased perfusion pressure. We could also observe the presence of protein inside the tubules and in glomerular spaces after renal histopathologic evaluation in the groups treated with the isolated components. However, only Gamma Toxin promoted an increase of the mesenteric bed perfusion pressure. The Natriuretic Peptide (0.03 and 0.1µg/mL) increased renal perfusion pressure. In addition, the natriuretic peptide increased cyclic guanosine monophosphate (cGMP) urinary excretion, but reduced electrolytes reabsorption in a dependent-concentration manner. The crude venom and the natriuretic peptide increased the arterial blood pressure, but decreased the hematocrit values, evaluated after in vivo experiments. However, the natriuretic peptide increased urinary flow and heartbeat frequency. In vivo renal function was evaluated by the clearance of inulin. The scorpion crude venom decreased the clearance of inulin, but this parameter was increased after natriuretic peptide treatment. The renal cortex blood flux, estimated by the clearance of p-aminohippurate, was reduced after the crude venom treatment. In conclusion, we demonstrated that Tityus serrulatus venom induced renal hemodynamic effects that were blocked in vitro by prasozin. In vivo experiments showed how the crude venom and its isolated components act increasing arterial blood pressure, heartbeat frequency and altered renal function.O veneno do escorpião Tityus serrulatus é uma mistura de peptídeos tóxicos e não tóxicos com diversas ações locais e sistêmicas. O objetivo deste trabalho foi estudar os efeitos cardiovasculares e renais induzidos pelo veneno total do escorpião T. serrulatus e de suas frações TsTx-V, Toxina γ e Natriurética. Foram utilizados ratos Wistar machos (250-300g) para os experimentos de perfusão de rim isolado, leito mesentérico, pressão arterial e perfusão in vivo. Para os ensaios de canal deferente foram utilizados camundongos Swiss (30-40g). O veneno de T. serrulatus apresentou efeito sobre o sistema nervoso autônomo observado através da contração do vaso deferente. O veneno total mostrou efeito adrenérgico demonstrado pela reversão dos seus efeitos renais após pré-tratamento dos rins com antagonista α-adrenérgico prazosin, especialmente sobre a resistência vascular renal (RVRVTs = 7,51 ± 0,96 vs RVRPz = 5,51 ± 0,43 mmHg/mL.g-1.min-1*,*p<0,05) e pressão de perfusão (PPVTs = 150,1 ± 18,40 vs PPPz = 118,1 ± 4,00 mmHg*,*p<0,05). As frações isoladas mostraram efeitos renais somatórios, haja visto que TsTx-V promoveu aumento da diurese e a Toxina γ causou efeitos pressóricos. Após avaliação histopatológica dos efeitos renais das frações isolados do veneno de T. serrulatus, observamos a presença de material protéico nos espaços urinários glomerulares e nos túbulos. Entretanto, no leito vascular mesentérico, somente a toxina γ mostrou-se ativa. Os efeitos renais induzidos pela fração natriurética (0,03 e 0,1µg/mL) revelaram aumento da pressão e, de maneira concentração-dependente, diminuição da reabsorção de eletrólitos e aumento da excreção urinária de guanosina monofosfato cíclico (GMPc). Nos experimentos in vivo, tanto o veneno total quanto a fração natriurética causaram aumento da pressão arterial média (PAM) e diminuição do hematócrito. Em adição, a fração natriurética causou ainda a elevação do fluxo urinário e da freqüência cardíaca. O clearance de inulina foi utilizado para a avaliação da função renal in vivo. O veneno total diminui significativamente o clearance da inulina, enquanto a fração natriurética causou elevação. O fluxo plasmático renal cortical, avaliado através do clearance de p-aminohipurato, foi reduzido por ação do veneno total de T. serrulatus. Em conclusão, o veneno de Tityus serrulatus promoveu efeitos hemodinâmicos renais que foram prontamente revertidos in vitro pelo prazosin. Os experimentos in vivo mostraram que o veneno de Tityus serrulatus induziu a elevação da pressão arterial média, taquicardia e alteração da função renal.Venenos de EscorpiãoTestes de Função RenalAntagonistas AdrenérgicosEfeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriuréticoBiological effects induced by Tityus serrulatus crude venom and its toxins TsTx-V, gamma toxin and natriuretic peptideinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/3840/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINAL2008_tese_rsalves.pdf2008_tese_rsalves.pdfapplication/pdf5032108http://repositorio.ufc.br/bitstream/riufc/3840/1/2008_tese_rsalves.pdf5ea41178c3160a3542ecbbb0db2c7c2dMD51riufc/38402019-10-25 14:01:20.611oai:repositorio.ufc.br:riufc/3840Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-25T17:01:20Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
dc.title.en.pt_BR.fl_str_mv Biological effects induced by Tityus serrulatus crude venom and its toxins TsTx-V, gamma toxin and natriuretic peptide
title Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
spellingShingle Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
Alves, Renata de Sousa
Venenos de Escorpião
Testes de Função Renal
Antagonistas Adrenérgicos
title_short Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
title_full Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
title_fullStr Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
title_full_unstemmed Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
title_sort Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético
author Alves, Renata de Sousa
author_facet Alves, Renata de Sousa
author_role author
dc.contributor.author.fl_str_mv Alves, Renata de Sousa
dc.contributor.advisor1.fl_str_mv Monteiro , Helena Serra Azul
contributor_str_mv Monteiro , Helena Serra Azul
dc.subject.por.fl_str_mv Venenos de Escorpião
Testes de Função Renal
Antagonistas Adrenérgicos
topic Venenos de Escorpião
Testes de Função Renal
Antagonistas Adrenérgicos
description The venom of Tityus serrulatus has a mixture of toxic and non toxic peptides presenting diverse systemic and local effects. The aim of this work was to investigate the cardiovascular and renal effects promoted by the crude venom of the scorpion Tityus serrulatus and its isolated components such as Tityus serrulatus toxin V (TsTx-V), Gamma Toxin and the newly isolated Natriuretic Peptide. The experiments of isolated perfused rat kidney, isolated mesenteric bed, arterial pressure and in vivo perfusion were performed using male Wistar rats weighing 250-300g. The assays with vas deferens were done using Swiss mice weighing 30-40g. The crude venom presented autonomic nervous system effects showed by the contraction of vas deferens. Adrenergic effects were demonstrated specially with the decrease of renal vascular resistance (RVRVTs = 7.51 ± 0.96 vs RVRPz = 5.51 ± 0.43 mmHg/mL.g-1.min-1*,*p<0.05) and renal perfusion pressure (PPVTs = 150.1 ± 18.40 vs PPPz = 118.1 ± 4.00 mmHg*,*p<0.05) induced by the crude venom after kidneys pre-treatment with prazosin. The venoms isolated components showed kidney addictional effects, where TsTx-V caused diuresis while Gamma Toxin increased perfusion pressure. We could also observe the presence of protein inside the tubules and in glomerular spaces after renal histopathologic evaluation in the groups treated with the isolated components. However, only Gamma Toxin promoted an increase of the mesenteric bed perfusion pressure. The Natriuretic Peptide (0.03 and 0.1µg/mL) increased renal perfusion pressure. In addition, the natriuretic peptide increased cyclic guanosine monophosphate (cGMP) urinary excretion, but reduced electrolytes reabsorption in a dependent-concentration manner. The crude venom and the natriuretic peptide increased the arterial blood pressure, but decreased the hematocrit values, evaluated after in vivo experiments. However, the natriuretic peptide increased urinary flow and heartbeat frequency. In vivo renal function was evaluated by the clearance of inulin. The scorpion crude venom decreased the clearance of inulin, but this parameter was increased after natriuretic peptide treatment. The renal cortex blood flux, estimated by the clearance of p-aminohippurate, was reduced after the crude venom treatment. In conclusion, we demonstrated that Tityus serrulatus venom induced renal hemodynamic effects that were blocked in vitro by prasozin. In vivo experiments showed how the crude venom and its isolated components act increasing arterial blood pressure, heartbeat frequency and altered renal function.
publishDate 2008
dc.date.issued.fl_str_mv 2008
dc.date.accessioned.fl_str_mv 2012-10-01T16:30:01Z
dc.date.available.fl_str_mv 2012-10-01T16:30:01Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv ALVES, R. de S. Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético. 2008. 188 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2008.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/3840
identifier_str_mv ALVES, R. de S. Efeitos biológicos induzidos pelo veneno total de Tityus serrulatus e suas frações TsTx-V, toxina gama e peptídeo natriurético. 2008. 188 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2008.
url http://www.repositorio.ufc.br/handle/riufc/3840
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