Efeito do tucumã (Astrocaryum aculeatum, Meyer) na citoproteção causada pelo estresse oxidativo e na modulação de células de leucemia promielocítica aguda

Detalhes bibliográficos
Ano de defesa: 2014
Autor(a) principal: Sagrillo, Michele Rorato lattes
Orientador(a): Cruz, Ivana Beatrice Mânica da lattes
Banca de defesa: Santos, Roberto Christ Vianna lattes, Barreto, Katia Padilha lattes, Fachinetto, Roselei lattes, Duarte, Marta Maria Medeiros Frescura lattes
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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spelling 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
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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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