Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS)
Ano de defesa: | 2015 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Farmacêuticas
|
Departamento: |
Análises Clínicas e Toxicológicas
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/17540 |
Resumo: | The thiosemicarbazone compounds are of considerable scientific interest because of their important biological and chemical properties, such as antitumor, antibacterial, antiviral, antiprotozoal, cytotoxic, among others. The compound salicylaldehyde-4-phenylthiosemicarbazone (SPTS), of the class of thiosemicarbazone, has promising pharmacological activities such as antioxidant and antitumor, thereby previous studies are needed to evaluate its toxicity. Thus, this study aimed to evaluate the toxicity in vitroof SPTS compound, through bioassay of Artemia salina in order to determine the median lethal concentration (LC50), activity of δ-aminolevulinate dehydratase (δ-ALA-D), thiol oxidase activity and assays of cell viability and genotoxicity. Acute and subacute toxicity tests of SPTS compound were also performed, using as methodology the Organization's guidelines for Coordination and Economic Development (OECD guidelines 423 and 407). In the analysis of acute toxicity, a single dose of 300 and, thereafter, 50 mg/kg SPTS was administered subcutaneously in rats, to evaluate the estimated mean lethal dose (LD50). In the study of subacute toxicity, SPTS compound was administered subcutaneously in animals at doses of 5, 10 and 20 mg/kg/day for 14 days. Biochemical, hematological and oxidative stress parameters were examined in the studies of acute and sub-acute toxicity, using samples of blood, kidney, liver and brain. Behavioral changes were analyzed in the subacute toxicity. In the results obtained inin vitroexperiments, was verified a LC50of 69,11μg/ml, being considered a compound active biologically, but there was no thiol oxidase effect or inhibition of δ-ALA-D. With respect to cell viability and genotoxicity assays, it was found that the concentration of 100μM significantly decreased cell viability and showed genotoxicity effects against cell culture. With regard to acute toxicity, the estimated LD50 was of 50-300 mg/kg. Moreover, acute exposure to 50 mg/kg of SPTS did not cause changes in biochemical and hematological parameters, but caused an increase in hepatic levels of ascorbic acid. In the assessment of subacute toxicity, however, numerous changes were observed as an increase in lipid peroxidation and in vitamin C and non-protein thiols levels in different tissues, as well as changes in glutathione S-transferase and catalase activities. We also observed behavioral changes in the open field test, decrease in body weight gain and increased levels of triglycerides. Thus, we conclude that the compound SPTS provided particularly subacute toxicity, since presented behavioural alterations, as well as changes in oxidative stress parameters and in the lipid profile. |
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2019-07-23T17:41:08Z2019-07-23T17:41:08Z2015-03-11http://repositorio.ufsm.br/handle/1/17540The thiosemicarbazone compounds are of considerable scientific interest because of their important biological and chemical properties, such as antitumor, antibacterial, antiviral, antiprotozoal, cytotoxic, among others. The compound salicylaldehyde-4-phenylthiosemicarbazone (SPTS), of the class of thiosemicarbazone, has promising pharmacological activities such as antioxidant and antitumor, thereby previous studies are needed to evaluate its toxicity. Thus, this study aimed to evaluate the toxicity in vitroof SPTS compound, through bioassay of Artemia salina in order to determine the median lethal concentration (LC50), activity of δ-aminolevulinate dehydratase (δ-ALA-D), thiol oxidase activity and assays of cell viability and genotoxicity. Acute and subacute toxicity tests of SPTS compound were also performed, using as methodology the Organization's guidelines for Coordination and Economic Development (OECD guidelines 423 and 407). In the analysis of acute toxicity, a single dose of 300 and, thereafter, 50 mg/kg SPTS was administered subcutaneously in rats, to evaluate the estimated mean lethal dose (LD50). In the study of subacute toxicity, SPTS compound was administered subcutaneously in animals at doses of 5, 10 and 20 mg/kg/day for 14 days. Biochemical, hematological and oxidative stress parameters were examined in the studies of acute and sub-acute toxicity, using samples of blood, kidney, liver and brain. Behavioral changes were analyzed in the subacute toxicity. In the results obtained inin vitroexperiments, was verified a LC50of 69,11μg/ml, being considered a compound active biologically, but there was no thiol oxidase effect or inhibition of δ-ALA-D. With respect to cell viability and genotoxicity assays, it was found that the concentration of 100μM significantly decreased cell viability and showed genotoxicity effects against cell culture. With regard to acute toxicity, the estimated LD50 was of 50-300 mg/kg. Moreover, acute exposure to 50 mg/kg of SPTS did not cause changes in biochemical and hematological parameters, but caused an increase in hepatic levels of ascorbic acid. In the assessment of subacute toxicity, however, numerous changes were observed as an increase in lipid peroxidation and in vitamin C and non-protein thiols levels in different tissues, as well as changes in glutathione S-transferase and catalase activities. We also observed behavioral changes in the open field test, decrease in body weight gain and increased levels of triglycerides. Thus, we conclude that the compound SPTS provided particularly subacute toxicity, since presented behavioural alterations, as well as changes in oxidative stress parameters and in the lipid profile.As tiossemicarbazonas são compostos de considerável interesse científico, devido as suas importantes propriedades químicas e biológicas, tais como antitumoral, antibacteriana, antiviral, antiprotozoária, citotóxica, dentre outras. O composto salicilaldeído-4-feniltiosemicarbazona (SPTS), da classe das tiossemicarbazonas, possui atividades farmacológicas promissoras como atividade antioxidante e antitumoral, deste modo são necessários estudos prévios para avaliar a sua toxicidade. Desta forma, este trabalho teve como objetivo avaliar a toxicidade in vitro do composto SPTS, através do bioensaio da Artemia salina com a finalidade de determinar a concentração letal média (CL50), atividade da δ- aminolevulinato desidratase (δ-ALA-D), atividade tiol oxidase e ensaios de viabilidade celular e genotoxicidade. Testes de toxicidade aguda e subaguda do composto SPTS também foram realizados, utilizando como metodologia as diretrizes da Organização para a Coordenação e Desenvolvimento Econômico (OECD diretrizes 423 e 407). Na análise da toxicidade aguda, uma única dose de 300 e, posteriormente, 50 mg/kg de SPTS foi administrada por via subcutânea em ratos machos, para avaliar a dose letal média estimada (DL50). No estudo de toxicidade subaguda, o composto SPTS foi administrado por via subcutânea nos animais em doses de 5, 10 e 20 mg/kg/dia durante 14 dias. Parâmetros bioquímicos, de estresse oxidativo e hematológicos foram analisados nos estudos de toxicidade aguda e subaguda, utilizando amostras de sangue, rins, fígado e cérebro. Alterações comportamentais foram analisadas na toxicidade subaguda. Nos resultados obtidos nos experimentosin vitro, foi verificada uma CL50 de 69,11μg/ml, sendo considerado um composto biologicamente ativo, mas não houve efeito tiol oxidase e nem inibição da δ-ALA-D. Em relação aos testes de viabilidade celular e genotoxicidade, foi verificado que a concentração de 100μM diminuiu significantemente a viabilidade celular e causou efeitos genotóxicos frente a cultura de células. Em relação a toxicidade aguda, a DL50 estimada foi de 50-300mg/kg. Além disso, a exposição aguda a 50 mg/kg de SPTS não causou alterações nos parâmetros bioquímicos e hematológicos, mas causou elevação nos níveis hepáticos de ácido ascórbico. Na avaliação da toxicidade subaguda, entretanto, inúmeras alterações foram observadas, como o aumento na peroxidação lipídica e nos níveis de vitamina C e tióis nãoproteicos em diferentes tecidos, bem como alterações nas atividades da glutationa S-transferase e catalase. Também foram observadas alterações comportamentais no teste do open field, diminuição no ganho de peso corporal e aumento nos níveis de triglicerídeos. Desta forma, nós concluímos que o composto SPTS apresentou especialmente toxicidade subaguda, uma vez que causou alterações comportamentais, nos parâmetros de estresse oxidativo e no perfil lipídico.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilAnálises Clínicas e ToxicológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessTiossemicarbazonasSPTSToxicidadeThiosemicarbazoneToxicityCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS)Assessment of the effects of compound toxicological salicylaldehyde-4-feniltiossemicarbazone (SPTS)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCampos, Marli Matiko Anraku dehttp://lattes.cnpq.br/6421182991125434Pinton, Simonehttp://lattes.cnpq.br/1205982002582299Puntel, Gustavo Orionehttp://lattes.cnpq.br/0319301096075015http://lattes.cnpq.br/1443563791005886Teixeira, Taiane Piccini400300000005600ac8e430f-6a47-4d8e-91cd-2fd828e1aa37f285a04d-ecbf-4fc4-9cfb-e0b955b473a957c0b38a-cf20-4af9-9d70-d0f9c2080b0a9833072d-6444-4c3b-b41b-e9c278dcd5c5reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
dc.title.alternative.eng.fl_str_mv |
Assessment of the effects of compound toxicological salicylaldehyde-4-feniltiossemicarbazone (SPTS) |
title |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
spellingShingle |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) Teixeira, Taiane Piccini Tiossemicarbazonas SPTS Toxicidade Thiosemicarbazone Toxicity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
title_full |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
title_fullStr |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
title_full_unstemmed |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
title_sort |
Avaliação dos efeitos toxicológicos do composto salicilaldeído-4-feniltiossemicarbazona (SPTS) |
author |
Teixeira, Taiane Piccini |
author_facet |
Teixeira, Taiane Piccini |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Campos, Marli Matiko Anraku de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6421182991125434 |
dc.contributor.referee1.fl_str_mv |
Pinton, Simone |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/1205982002582299 |
dc.contributor.referee2.fl_str_mv |
Puntel, Gustavo Orione |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0319301096075015 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1443563791005886 |
dc.contributor.author.fl_str_mv |
Teixeira, Taiane Piccini |
contributor_str_mv |
Campos, Marli Matiko Anraku de Pinton, Simone Puntel, Gustavo Orione |
dc.subject.por.fl_str_mv |
Tiossemicarbazonas SPTS Toxicidade |
topic |
Tiossemicarbazonas SPTS Toxicidade Thiosemicarbazone Toxicity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Thiosemicarbazone Toxicity |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
The thiosemicarbazone compounds are of considerable scientific interest because of their important biological and chemical properties, such as antitumor, antibacterial, antiviral, antiprotozoal, cytotoxic, among others. The compound salicylaldehyde-4-phenylthiosemicarbazone (SPTS), of the class of thiosemicarbazone, has promising pharmacological activities such as antioxidant and antitumor, thereby previous studies are needed to evaluate its toxicity. Thus, this study aimed to evaluate the toxicity in vitroof SPTS compound, through bioassay of Artemia salina in order to determine the median lethal concentration (LC50), activity of δ-aminolevulinate dehydratase (δ-ALA-D), thiol oxidase activity and assays of cell viability and genotoxicity. Acute and subacute toxicity tests of SPTS compound were also performed, using as methodology the Organization's guidelines for Coordination and Economic Development (OECD guidelines 423 and 407). In the analysis of acute toxicity, a single dose of 300 and, thereafter, 50 mg/kg SPTS was administered subcutaneously in rats, to evaluate the estimated mean lethal dose (LD50). In the study of subacute toxicity, SPTS compound was administered subcutaneously in animals at doses of 5, 10 and 20 mg/kg/day for 14 days. Biochemical, hematological and oxidative stress parameters were examined in the studies of acute and sub-acute toxicity, using samples of blood, kidney, liver and brain. Behavioral changes were analyzed in the subacute toxicity. In the results obtained inin vitroexperiments, was verified a LC50of 69,11μg/ml, being considered a compound active biologically, but there was no thiol oxidase effect or inhibition of δ-ALA-D. With respect to cell viability and genotoxicity assays, it was found that the concentration of 100μM significantly decreased cell viability and showed genotoxicity effects against cell culture. With regard to acute toxicity, the estimated LD50 was of 50-300 mg/kg. Moreover, acute exposure to 50 mg/kg of SPTS did not cause changes in biochemical and hematological parameters, but caused an increase in hepatic levels of ascorbic acid. In the assessment of subacute toxicity, however, numerous changes were observed as an increase in lipid peroxidation and in vitamin C and non-protein thiols levels in different tissues, as well as changes in glutathione S-transferase and catalase activities. We also observed behavioral changes in the open field test, decrease in body weight gain and increased levels of triglycerides. Thus, we conclude that the compound SPTS provided particularly subacute toxicity, since presented behavioural alterations, as well as changes in oxidative stress parameters and in the lipid profile. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-03-11 |
dc.date.accessioned.fl_str_mv |
2019-07-23T17:41:08Z |
dc.date.available.fl_str_mv |
2019-07-23T17:41:08Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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http://repositorio.ufsm.br/handle/1/17540 |
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http://repositorio.ufsm.br/handle/1/17540 |
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por |
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por |
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400300000005 |
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600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Análises Clínicas e Toxicológicas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
|
_version_ |
1794524387414638592 |