Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda
Ano de defesa: | 2014 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/3860 |
Resumo: | Carotenoids are natural pigments soluble inversely associated with risk of a variety of diseases. In the Amazon region there is a wide variety of native fruits which are rich in carotenoids, which functional properties need to be clarified. This is the case of the fiber palm fruits (Astrocaryum aculeatum Mart.), regionally consumed. Therefore, we investigated the protective effects of ethanol extract isolated from the peel and the pulp of fruits tucumã against cytotoxicity and DNA damage induced by H2O2 in human lymphocytes and antiproliferative activity against the same cell lineage Acute Promyelocytic Leukemia (APL), NB4- APL, with and without concurrent exposure to all-trans retinoic acid (ATRA), drug used for the treatment of APL, thus constituting the subjects of the first and second article of this thesis. Firstly, the main chemical compounds present in the extracts were determined by chromatographic and spectrophotometric methods. The bark extract showed higher concentration of total polyphenols, flavonoids, alkaloids, tannins, β-carotene and quercetin than extract pulp of tucumã . Cultures of human lymphocytes with and without H2O2 and NB4 cells, APL was obtained after 72h and cell viability assay Picogreen® DNA, as well as the activity of caspase 1, 3 and 8 related to events of apoptosis was assessed by immunoassay tests. In cultures of human lymphocytes with and without H2O2 treated with the extracts of the skin and pulp of the present tucumã showed that both cytologic and genoprotetor effect especially in intermediate doses (300 to 900 ug / ml) when compared to lower and higher concentrations. The extracts were able to largely decrease the activity of caspases 1, 3 and 8 which were higher in cells exposed to H2O2. These results suggest a positive effect of tucumã in cells exposed to toxic compounds. When submitted to culture the LPA-NB4 cells to the treatment with the ethanolic extract of the pulp and the peel of tucumã 72 hours after the cell proliferation in concentrations greater than 600 mg / ml was effective at inhibiting cell proliferation. When NB4 cells were treated with ATRA showed a strong inhibitory effect as expected (14.5 ± 2.7% of control). Despite extracts also present tucumã antiproliferative effect on NB4 cells, this effect was more moderate than ATRA. The levels of caspases tested were shown to be higher in extracts of ATRA and tucumã indicating that it can trigger apoptosis in NB4 cells. These results suggest that fruits rich in retinoids may have cytotoxic effects against APL cells. |
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2016-10-062016-10-062014-12-17SAGRILLO, Michele Rorato. EFFECT OF TUCUMÃ FRUIT (Astrocaryum aculeatum, MEYER) IN THE CYTOPROTECTION CAUSED BY THE OXIDATIVE STRESS AND IN THE MODULATION OF CELLS OF ACCUTE PROMYELOCYTIC LEUKEMIA. 2014. 95 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/3860Carotenoids are natural pigments soluble inversely associated with risk of a variety of diseases. In the Amazon region there is a wide variety of native fruits which are rich in carotenoids, which functional properties need to be clarified. This is the case of the fiber palm fruits (Astrocaryum aculeatum Mart.), regionally consumed. Therefore, we investigated the protective effects of ethanol extract isolated from the peel and the pulp of fruits tucumã against cytotoxicity and DNA damage induced by H2O2 in human lymphocytes and antiproliferative activity against the same cell lineage Acute Promyelocytic Leukemia (APL), NB4- APL, with and without concurrent exposure to all-trans retinoic acid (ATRA), drug used for the treatment of APL, thus constituting the subjects of the first and second article of this thesis. Firstly, the main chemical compounds present in the extracts were determined by chromatographic and spectrophotometric methods. The bark extract showed higher concentration of total polyphenols, flavonoids, alkaloids, tannins, β-carotene and quercetin than extract pulp of tucumã . Cultures of human lymphocytes with and without H2O2 and NB4 cells, APL was obtained after 72h and cell viability assay Picogreen® DNA, as well as the activity of caspase 1, 3 and 8 related to events of apoptosis was assessed by immunoassay tests. In cultures of human lymphocytes with and without H2O2 treated with the extracts of the skin and pulp of the present tucumã showed that both cytologic and genoprotetor effect especially in intermediate doses (300 to 900 ug / ml) when compared to lower and higher concentrations. The extracts were able to largely decrease the activity of caspases 1, 3 and 8 which were higher in cells exposed to H2O2. These results suggest a positive effect of tucumã in cells exposed to toxic compounds. When submitted to culture the LPA-NB4 cells to the treatment with the ethanolic extract of the pulp and the peel of tucumã 72 hours after the cell proliferation in concentrations greater than 600 mg / ml was effective at inhibiting cell proliferation. When NB4 cells were treated with ATRA showed a strong inhibitory effect as expected (14.5 ± 2.7% of control). Despite extracts also present tucumã antiproliferative effect on NB4 cells, this effect was more moderate than ATRA. The levels of caspases tested were shown to be higher in extracts of ATRA and tucumã indicating that it can trigger apoptosis in NB4 cells. These results suggest that fruits rich in retinoids may have cytotoxic effects against APL cells.Os carotenoides são pigmentos naturais solúveis inversamente associados com o risco de uma variedade de doenças. Na região da Amazônia há uma grande variedade frutos nativos ricos em carotenoides, cujas propriedades funcionais precisam ser esclarecidas. Este é o caso dos frutos de palmeira tucumã (Astrocaryum aculeatum Mart.), regionalmente consumido. Portanto, nós investigamos os efeitos protetores do extrato etanólico isolados de casca e polpa de frutas tucumã contra citotoxicidade e dano ao DNA induzido por H2O2 em linfócitos humanos e a atividade antiproliferativa dos mesmos frente a linhagem celular de Leucemia Promielocítica Aguda (LPA), NB4-LPA, com e sem exposição concomitante ao ácido alltrans- retinóico (ATRA), fármaco utilizado para o tratamento da LPA, constituindo assim os temas do primeiro e segundo artigo da tese. Em primeiro lugar, os compostos químicos principais presentes nos extratos foram determinados através de métodos cromatográficos e espectrofotométrico. O extrato da casca apresentou maior concentração de polifenois totais, flavonoides, alcaloides, taninos, β-caroteno e quercetina do que extrato de polpa de tucumã. As culturas de linfócitos humanos, com e sem H2O2 e as células NB4-LPA foram obtidas após 72h e a viabilidade das células, o ensaio do DNA Picogreen®, assim como a atividade das caspase 1, 3 e 8 relacionadas com acontecimentos de apoptose foi avaliada por meio de testes de imunoensaio. Nas culturas de linfócitos humanos, com e sem H2O2 tratados com os extratos obtidos da casca e da polpa do tucumã mostraram que ambos apresentaram efeito cito e genoprotetor principalmente em doses intermediárias (300 a 900 μg/mL) quando comparado com concentrações inferiores e superiores. Os extratos foram capazes de diminuir a grande parte da atividade das caspases 1, 3 e 8 que eram mais elevadas em células expostas a H2O2. Estes resultados sugerem efeito positivo do tucumã em células expostas a compostos tóxicos. Quando submetemos à cultura as células NB4-LPA frente ao tratamento com os extratos etanólicos da polpa e casca do tucumã depois de 72h a proliferação celular nas concentrações maiores que 600 μg/mL foram eficazes para inibir a proliferação celular. Quando as células NB4 foram tratadas apenas com ATRA mostrou-se um forte efeito inibitório como esperado (14,5 ± 2,7% do grupo controle). Apesar dos extratos do tucumã também apresentarem efeito antiproliferativo sobre células NB4, este efeito foi mais moderado do que o ATRA. Os níveis das caspases testadas mostraram-se altas na presença de extratos de tucumã e ATRA indicando que o tucumã é capaz de desencadear apoptose em células NB4. Estes resultados sugerem que frutas ricas em retinoides podem apresentar efeito citotóxico contra células de LPA.application/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaAstrocaryum aculeatuCarotenoidesCultura de linfócitosDanos de DNAAstrocaryum aculeatumCarotenoidsCulture of lymphocytesDNA damageCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAEfeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica agudaEffect of tucumã fruit (Astrocaryum aculeatum, Meyer) in the cytoprotection caused by the oxidative stress and in the modulation of cells of acute promyelocytic leukemiainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCruz, Ivana Beatrice Mânica dahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4790333D6Santos, Roberto Christ Viannahttp://lattes.cnpq.br/9176719594431835Barreto, Katia Padilhahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4727510Z9Fachinetto, Roseleihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2Duarte, Marta Maria Medeiros Frescurahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4775081J6http://lattes.cnpq.br/2566285176244747Sagrillo, Michele Rorato2010000000004003003003003003003000b5fcfe0-b017-4163-80e2-17c110fbcf01d0fc9d7e-5638-468e-b4e4-fb607cfe4575a269af39-b3ff-4399-b1b5-aa61351e6aaf7d233f19-66ff-4aca-a9fc-784eddf6b946ac49375d-6301-42f1-adc2-c0c475db11fcca139a66-990f-40fc-9fe9-c24e2cd83c8ainfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALSAGRILLO, MICHELE RORATO.pdfTese de Doutoradoapplication/pdf2595037http://repositorio.ufsm.br/bitstream/1/3860/1/SAGRILLO%2c%20MICHELE%20RORATO.pdf706d93dc72528b388843916e638fef15MD51TEXTSAGRILLO, MICHELE RORATO.pdf.txtSAGRILLO, MICHELE RORATO.pdf.txtExtracted texttext/plain208125http://repositorio.ufsm.br/bitstream/1/3860/2/SAGRILLO%2c%20MICHELE%20RORATO.pdf.txt2c57cd7f5851c60ad519fc9636602eaaMD52THUMBNAILSAGRILLO, MICHELE RORATO.pdf.jpgSAGRILLO, MICHELE RORATO.pdf.jpgIM Thumbnailimage/jpeg5079http://repositorio.ufsm.br/bitstream/1/3860/3/SAGRILLO%2c%20MICHELE%20RORATO.pdf.jpg35aa13baf4d3ef1251d40516bb5447a6MD531/38602017-09-11 14:26:46.818oai:repositorio.ufsm.br:1/3860Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-09-11T17:26:46Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
dc.title.alternative.eng.fl_str_mv |
Effect of tucumã fruit (Astrocaryum aculeatum, Meyer) in the cytoprotection caused by the oxidative stress and in the modulation of cells of acute promyelocytic leukemia |
title |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
spellingShingle |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda Sagrillo, Michele Rorato Astrocaryum aculeatu Carotenoides Cultura de linfócitos Danos de DNA Astrocaryum aculeatum Carotenoids Culture of lymphocytes DNA damage CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
title_full |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
title_fullStr |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
title_full_unstemmed |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
title_sort |
Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda |
author |
Sagrillo, Michele Rorato |
author_facet |
Sagrillo, Michele Rorato |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cruz, Ivana Beatrice Mânica da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4790333D6 |
dc.contributor.referee1.fl_str_mv |
Santos, Roberto Christ Vianna |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/9176719594431835 |
dc.contributor.referee2.fl_str_mv |
Barreto, Katia Padilha |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4727510Z9 |
dc.contributor.referee3.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2 |
dc.contributor.referee4.fl_str_mv |
Duarte, Marta Maria Medeiros Frescura |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4775081J6 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2566285176244747 |
dc.contributor.author.fl_str_mv |
Sagrillo, Michele Rorato |
contributor_str_mv |
Cruz, Ivana Beatrice Mânica da Santos, Roberto Christ Vianna Barreto, Katia Padilha Fachinetto, Roselei Duarte, Marta Maria Medeiros Frescura |
dc.subject.por.fl_str_mv |
Astrocaryum aculeatu Carotenoides Cultura de linfócitos Danos de DNA |
topic |
Astrocaryum aculeatu Carotenoides Cultura de linfócitos Danos de DNA Astrocaryum aculeatum Carotenoids Culture of lymphocytes DNA damage CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Astrocaryum aculeatum Carotenoids Culture of lymphocytes DNA damage |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Carotenoids are natural pigments soluble inversely associated with risk of a variety of diseases. In the Amazon region there is a wide variety of native fruits which are rich in carotenoids, which functional properties need to be clarified. This is the case of the fiber palm fruits (Astrocaryum aculeatum Mart.), regionally consumed. Therefore, we investigated the protective effects of ethanol extract isolated from the peel and the pulp of fruits tucumã against cytotoxicity and DNA damage induced by H2O2 in human lymphocytes and antiproliferative activity against the same cell lineage Acute Promyelocytic Leukemia (APL), NB4- APL, with and without concurrent exposure to all-trans retinoic acid (ATRA), drug used for the treatment of APL, thus constituting the subjects of the first and second article of this thesis. Firstly, the main chemical compounds present in the extracts were determined by chromatographic and spectrophotometric methods. The bark extract showed higher concentration of total polyphenols, flavonoids, alkaloids, tannins, β-carotene and quercetin than extract pulp of tucumã . Cultures of human lymphocytes with and without H2O2 and NB4 cells, APL was obtained after 72h and cell viability assay Picogreen® DNA, as well as the activity of caspase 1, 3 and 8 related to events of apoptosis was assessed by immunoassay tests. In cultures of human lymphocytes with and without H2O2 treated with the extracts of the skin and pulp of the present tucumã showed that both cytologic and genoprotetor effect especially in intermediate doses (300 to 900 ug / ml) when compared to lower and higher concentrations. The extracts were able to largely decrease the activity of caspases 1, 3 and 8 which were higher in cells exposed to H2O2. These results suggest a positive effect of tucumã in cells exposed to toxic compounds. When submitted to culture the LPA-NB4 cells to the treatment with the ethanolic extract of the pulp and the peel of tucumã 72 hours after the cell proliferation in concentrations greater than 600 mg / ml was effective at inhibiting cell proliferation. When NB4 cells were treated with ATRA showed a strong inhibitory effect as expected (14.5 ± 2.7% of control). Despite extracts also present tucumã antiproliferative effect on NB4 cells, this effect was more moderate than ATRA. The levels of caspases tested were shown to be higher in extracts of ATRA and tucumã indicating that it can trigger apoptosis in NB4 cells. These results suggest that fruits rich in retinoids may have cytotoxic effects against APL cells. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-12-17 |
dc.date.accessioned.fl_str_mv |
2016-10-06 |
dc.date.available.fl_str_mv |
2016-10-06 |
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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doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SAGRILLO, Michele Rorato. EFFECT OF TUCUMÃ FRUIT (Astrocaryum aculeatum, MEYER) IN THE CYTOPROTECTION CAUSED BY THE OXIDATIVE STRESS AND IN THE MODULATION OF CELLS OF ACCUTE PROMYELOCYTIC LEUKEMIA. 2014. 95 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/3860 |
identifier_str_mv |
SAGRILLO, Michele Rorato. EFFECT OF TUCUMÃ FRUIT (Astrocaryum aculeatum, MEYER) IN THE CYTOPROTECTION CAUSED BY THE OXIDATIVE STRESS AND IN THE MODULATION OF CELLS OF ACCUTE PROMYELOCYTIC LEUKEMIA. 2014. 95 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
url |
http://repositorio.ufsm.br/handle/1/3860 |
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Farmacologia |
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