Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFLA |
Texto Completo: | http://repositorio.ufla.br/jspui/handle/1/12782 |
Resumo: | Phenolic compounds have pharmacological activities that contemplate mechanisms of inhibition or inductions of DNA molecules degradation. Genotoxic damages can be induced by venom or occur naturally. Natural compounds can act as enzymatic inhibitors through a connection to hydrophobic sites present in the structures of some enzymes or to catalytic sites, neutralization of reactive species or suppression of their generation, sequestration of ions corresponding to enzymatic cofactors, or competition for solvation water of enzymes triggering the precipitation and inactivation of these enzymes. Aiming to investigate the protective action of phenolic compounds, caffeic acid (AC), gallic acid (GA), syringic acid (AS) and vanillic acid (AV) on enzyme induced cytogenetic damage were used as tools to induce venom Bothrops atrox, B. jararacussu and Lachesis muta muta. The electrophoretic profile (SDS-PAGE) of incubations containing venoms and phenolic compounds suggests the presence of molecular interactions of these, with toxins present in venoms. Agarose gel electrophoresis allowed to evaluate the human leukocyte DNA fragmentation induced by snake venoms as well as the antigenotoxic action of phenolic acids when previously incubated with venoms. The comet test performed with human leukocytes showed that the phenolic compounds evaluated, in high doses, can induce DNA fragmentation as well as potentiate the genotoxic action exerted by the toxins present in the venoms. In the Krebs cycle succinate dehydrogenase inhibition assay, CA and GA acted to potentiate inhibition the action of malic acid in some at doses, whereas for AS and AV, there were no significant differences in potentiation or reversal of inhibition caused by the inhibitor (malonate) on a succinate dehydrogenase. The partial characterization of these compounds, carried out in the present work, complements previous studies on these molecules that have high potential for future therapeutic applications, and it is also necessary to prospect formulations and safe administration forms for human consumption, since safe daily consumption values have already been previously defined by ANVISA. The activities evaluated in the present study suggest possible applications of these compounds alone, or plant extracts that present these molecules in their composition, in the complementation of traditional antiophidic serum therapy or in its substitution, as well as in the prevention and treatment of inflammatory, digestive, neurodegenerative and several others that are associated to the action of proteases, phospholipases and oxidases in general of great value in the medical-scientific scope. |
id |
UFLA_74e23afe2a913c276169e89ca2c9e5bc |
---|---|
oai_identifier_str |
oai:localhost:1/12782 |
network_acronym_str |
UFLA |
network_name_str |
Repositório Institucional da UFLA |
repository_id_str |
|
spelling |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danosEvaluation of antigenotoxic and anticytotoxic potential of phenolic compounds using snake venoms as damage-inducing toolsInibidores enzimáticosÁcidos fenólicosPeçonhas de serpentesSuccinato desidrogenaseEnzyme inhibitorsPhenolic acidSnake venomsSuccinate dehydrogenaseQuímicaPhenolic compounds have pharmacological activities that contemplate mechanisms of inhibition or inductions of DNA molecules degradation. Genotoxic damages can be induced by venom or occur naturally. Natural compounds can act as enzymatic inhibitors through a connection to hydrophobic sites present in the structures of some enzymes or to catalytic sites, neutralization of reactive species or suppression of their generation, sequestration of ions corresponding to enzymatic cofactors, or competition for solvation water of enzymes triggering the precipitation and inactivation of these enzymes. Aiming to investigate the protective action of phenolic compounds, caffeic acid (AC), gallic acid (GA), syringic acid (AS) and vanillic acid (AV) on enzyme induced cytogenetic damage were used as tools to induce venom Bothrops atrox, B. jararacussu and Lachesis muta muta. The electrophoretic profile (SDS-PAGE) of incubations containing venoms and phenolic compounds suggests the presence of molecular interactions of these, with toxins present in venoms. Agarose gel electrophoresis allowed to evaluate the human leukocyte DNA fragmentation induced by snake venoms as well as the antigenotoxic action of phenolic acids when previously incubated with venoms. The comet test performed with human leukocytes showed that the phenolic compounds evaluated, in high doses, can induce DNA fragmentation as well as potentiate the genotoxic action exerted by the toxins present in the venoms. In the Krebs cycle succinate dehydrogenase inhibition assay, CA and GA acted to potentiate inhibition the action of malic acid in some at doses, whereas for AS and AV, there were no significant differences in potentiation or reversal of inhibition caused by the inhibitor (malonate) on a succinate dehydrogenase. The partial characterization of these compounds, carried out in the present work, complements previous studies on these molecules that have high potential for future therapeutic applications, and it is also necessary to prospect formulations and safe administration forms for human consumption, since safe daily consumption values have already been previously defined by ANVISA. The activities evaluated in the present study suggest possible applications of these compounds alone, or plant extracts that present these molecules in their composition, in the complementation of traditional antiophidic serum therapy or in its substitution, as well as in the prevention and treatment of inflammatory, digestive, neurodegenerative and several others that are associated to the action of proteases, phospholipases and oxidases in general of great value in the medical-scientific scope.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Os compostos fenólicos têm atividades farmacológicas que contemplam mecanismos de inibição ou indução da degradação de moléculas de DNA. Danos genotóxicos podem ocorrer naturalmente ou ser induzidos por peçonhas. Compostos naturais podem atuar como inibidores enzimáticos através de ligação a sítios hidrofóbicos presentes nas estruturas de algumas enzimas ou a sítios catalíticos, neutralização de espécies reativas ou supressão de sua geração, sequestro de íons que correspondem a cofatores enzimáticos, ou ainda competição pela água de solvatação de enzimas desencadeando a precipitação e inativação destas. Visando prospectar a ação protetora dos compostos fenólicos, ácido cafeico (AC), ácido gálico (AG), ácido siríngico (AS) e ácido vanílico (AV) sobre danos citogenéticos induzidos por enzimas, foram utilizadas como ferramentas indutoras de danos peçonhas de serpentes das espécies Bothrops atrox, B. jararacussu e Lachesis muta muta. O perfil eletroforético (SDS-PAGE) de incubados contendo peçonhas e compostos fenólicos sugere a presença de interações moleculares destes com toxinas presentes nas peçonhas. Eletroforeses em gel de agarose permitiram avaliar a fragmentação de DNA de leucócitos humanos induzida pelas peçonhas de serpentes assim como a ação antigenotóxica exercida pelos ácidos fenólicos, quando previamente incubados com as peçonhas. O teste cometa realizado com leucócitos humanos mostrou que os compostos fenólicos avaliados, em altas doses, podem induzir fragmentação do DNA potencializando a ação genotóxica exercida pelas toxinas presentes nas peçonhas. No ensaio de inibição da succinato desidrogenase, o AC e AG potencializaram a inibição exercida pelo ácido malônico em algumas doses, enquanto que para o AS e AV não foram observadas diferenças significativas na potencialização ou reversão da inibição causada pelo inibidor (malonato) sobre a succinato desidrogenase. A caracterização parcial destes compostos, realizada no presente trabalho, complementa estudos prévios sobre estas moléculas que possuem alto potencial para futuras aplicações terapêuticas, sendo necessário ainda prospectar formulações e formas de administração seguras para consumo humano, uma vez que valores seguros de consumo diário por meio de alimentos, bebidas ou produtos nutracêuticos já foram previamente definidos pela ANVISA. As atividades avaliadas (citotoxicidade e genotoxicidade) no presente trabalho sugerem possíveis aplicações destes compostos, isoladamente ou de extratos vegetais que apresentem estas moléculas em sua composição, na complementação da soroterapia antiofídica tradicional ou em sua substituição, assim como na prevenção e tratamento de doenças inflamatórias, digestivas, neurodegenerativas e diversas outras que estejam associadas à ação de proteases, fosfolipases e oxidases em geral de grande valia no âmbito médico-científico.Universidade Federal de LavrasPrograma de Pós-Graduação em AgroquímicaUFLAbrasilDepartamento de QuímicaMarcussi, SilvanaSimão, Anderson AssaidPereira, Luciana Lopes SilvaCunha, Elaine Fontes Ferreira daSantos Filho, Norival AlvesAbreu, Tatiane Silva de2017-04-28T12:38:18Z2017-04-28T12:38:18Z2017-04-282017-03-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfABREU, T. S. de. Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos. 2017. 102 p. Dissertação (Mestrado em Agroquímica)-Universidade Federal de Lavras, Lavras, 2017.http://repositorio.ufla.br/jspui/handle/1/12782porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFLAinstname:Universidade Federal de Lavras (UFLA)instacron:UFLA2018-05-08T18:44:20Zoai:localhost:1/12782Repositório InstitucionalPUBhttp://repositorio.ufla.br/oai/requestnivaldo@ufla.br || repositorio.biblioteca@ufla.bropendoar:2018-05-08T18:44:20Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA)false |
dc.title.none.fl_str_mv |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos Evaluation of antigenotoxic and anticytotoxic potential of phenolic compounds using snake venoms as damage-inducing tools |
title |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos |
spellingShingle |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos Abreu, Tatiane Silva de Inibidores enzimáticos Ácidos fenólicos Peçonhas de serpentes Succinato desidrogenase Enzyme inhibitors Phenolic acid Snake venoms Succinate dehydrogenase Química |
title_short |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos |
title_full |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos |
title_fullStr |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos |
title_full_unstemmed |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos |
title_sort |
Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos |
author |
Abreu, Tatiane Silva de |
author_facet |
Abreu, Tatiane Silva de |
author_role |
author |
dc.contributor.none.fl_str_mv |
Marcussi, Silvana Simão, Anderson Assaid Pereira, Luciana Lopes Silva Cunha, Elaine Fontes Ferreira da Santos Filho, Norival Alves |
dc.contributor.author.fl_str_mv |
Abreu, Tatiane Silva de |
dc.subject.por.fl_str_mv |
Inibidores enzimáticos Ácidos fenólicos Peçonhas de serpentes Succinato desidrogenase Enzyme inhibitors Phenolic acid Snake venoms Succinate dehydrogenase Química |
topic |
Inibidores enzimáticos Ácidos fenólicos Peçonhas de serpentes Succinato desidrogenase Enzyme inhibitors Phenolic acid Snake venoms Succinate dehydrogenase Química |
description |
Phenolic compounds have pharmacological activities that contemplate mechanisms of inhibition or inductions of DNA molecules degradation. Genotoxic damages can be induced by venom or occur naturally. Natural compounds can act as enzymatic inhibitors through a connection to hydrophobic sites present in the structures of some enzymes or to catalytic sites, neutralization of reactive species or suppression of their generation, sequestration of ions corresponding to enzymatic cofactors, or competition for solvation water of enzymes triggering the precipitation and inactivation of these enzymes. Aiming to investigate the protective action of phenolic compounds, caffeic acid (AC), gallic acid (GA), syringic acid (AS) and vanillic acid (AV) on enzyme induced cytogenetic damage were used as tools to induce venom Bothrops atrox, B. jararacussu and Lachesis muta muta. The electrophoretic profile (SDS-PAGE) of incubations containing venoms and phenolic compounds suggests the presence of molecular interactions of these, with toxins present in venoms. Agarose gel electrophoresis allowed to evaluate the human leukocyte DNA fragmentation induced by snake venoms as well as the antigenotoxic action of phenolic acids when previously incubated with venoms. The comet test performed with human leukocytes showed that the phenolic compounds evaluated, in high doses, can induce DNA fragmentation as well as potentiate the genotoxic action exerted by the toxins present in the venoms. In the Krebs cycle succinate dehydrogenase inhibition assay, CA and GA acted to potentiate inhibition the action of malic acid in some at doses, whereas for AS and AV, there were no significant differences in potentiation or reversal of inhibition caused by the inhibitor (malonate) on a succinate dehydrogenase. The partial characterization of these compounds, carried out in the present work, complements previous studies on these molecules that have high potential for future therapeutic applications, and it is also necessary to prospect formulations and safe administration forms for human consumption, since safe daily consumption values have already been previously defined by ANVISA. The activities evaluated in the present study suggest possible applications of these compounds alone, or plant extracts that present these molecules in their composition, in the complementation of traditional antiophidic serum therapy or in its substitution, as well as in the prevention and treatment of inflammatory, digestive, neurodegenerative and several others that are associated to the action of proteases, phospholipases and oxidases in general of great value in the medical-scientific scope. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-04-28T12:38:18Z 2017-04-28T12:38:18Z 2017-04-28 2017-03-10 |
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 |
ABREU, T. S. de. Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos. 2017. 102 p. Dissertação (Mestrado em Agroquímica)-Universidade Federal de Lavras, Lavras, 2017. http://repositorio.ufla.br/jspui/handle/1/12782 |
identifier_str_mv |
ABREU, T. S. de. Potencial antigenotóxico e anticitotóxico de compostos fenólicos utilizando peçonhas de serpentes como ferramentas indutoras de danos. 2017. 102 p. Dissertação (Mestrado em Agroquímica)-Universidade Federal de Lavras, Lavras, 2017. |
url |
http://repositorio.ufla.br/jspui/handle/1/12782 |
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 Lavras Programa de Pós-Graduação em Agroquímica UFLA brasil Departamento de Química |
publisher.none.fl_str_mv |
Universidade Federal de Lavras Programa de Pós-Graduação em Agroquímica UFLA brasil Departamento de Química |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFLA instname:Universidade Federal de Lavras (UFLA) instacron:UFLA |
instname_str |
Universidade Federal de Lavras (UFLA) |
instacron_str |
UFLA |
institution |
UFLA |
reponame_str |
Repositório Institucional da UFLA |
collection |
Repositório Institucional da UFLA |
repository.name.fl_str_mv |
Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA) |
repository.mail.fl_str_mv |
nivaldo@ufla.br || repositorio.biblioteca@ufla.br |
_version_ |
1815439058663374848 |