Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos

Detalhes bibliográficos
Autor(a) principal: Lopes, Alan de Aguiar
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/7837
Resumo: Chronic obstructive pulmonary disease (DPOC) causes a respiratory capacity reduction and its development is be associated with cigarette smoke. Cigarette has more than 4800 toxic substances in your composition and it causes death of six million people in the world. Studies had been made to find methods to change cigarette-induced health problems. Propolis (P) has been reported as a natural product with several properties. Here, we used two types of experiments, in vitro and in vivo, to study the potential antioxidant use of P. Phytochemical analyze was made to evaluate which compounds are within P. Murine macrophages, RAW 264.7 cell line, are exposed to different concentrations of propolis and following analyses were made: total polyphenols levels; cell viability (MTT); reduction potential (DPPH); total reactive oxygen species levels (ROS) and malondialdehyde (MDA). Thirty C57BL6 mice were divided into 3 groups: Control+P, CS and CS+P. Both CS groups were exposed to 6 cigarettes per day for 5 days. CS group was treated with vehicle. Lung and bronchoalveolar lavage (BAL) were collected for histological analysis and differential cell counts. Analysis for mieloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), oxidized glutathione (GSSG), MDA, nitrite and western blotting for TNF-alpha were performed. Phytochemical analyses of P showed which possesses four main compounds: hydrocinnamic and coumaric acids; artepillin C and drupanin. P showed an increase in total polyphenols (p<0.001), cell viability (p<0.001) and DPPH levels (p<0.001) in concentration-dependent manner, different from MDA (p<0.001) which was inverse pattern. P decreased ROS levels in 15.6 and 31.2 mg/mL groups (p<0.05). Lung histology of Control+P group was similar to CS and CS+P groups, however significant inflammatory cell influx was observed in CS group. Propolis administration reduced significantly macrophages and neutrophils compared with CS group (p<0.01 e p<0.001, respectively). MPO levels was increased in CS (526.5±34.72 mU/mg ptn, p<0.01), but was shown to be reduced in CS+P (385.1±27.64 mU/mg ptn, p<0.05) compared with Control+P (134±12.99 mU/mg ptn, p<0.001), similar pattern was found in antioxidant enzymes: SOD (Controle+P: 523.5±29.6 U/mg ptn; CS: 523.5±29.6 U/mg ptn, p<0.001; CS+P: 246.8±15.69 U/mg ptn, p<0.001), CAT (Controle+P: 37.38±3.39 U/mg ptn; CS: 92.68±6.24 U/mg ptn, p<0.001; CS+P: 59.84±4.55 U/mg ptn, p<0.05) and GPx (Controle+P: 2.23±0.17 (µM/min/mg ptn) x 10-1; CS: 4.51±0.31 (µM/min/mg ptn) x 10-1, p<0.001; CS+P: 2.64±0.19 (µM/min/mg ptn) x 10-1, p<0.05) and different from GSH/GSSG ratio (Controle+P: 1.088±0.17; CS: 0.736±0.07, p<0.05; CS+P: 1.258±0.10, p<0.05). MDA (Controle+P: 0.266±0.05 nMol/mg ptn; CS: 0.94±0.076 nMol/mg ptn, p<0.001; CS+P: 0.498±0.06 nMol/mg ptn, p<0.01) and nitrite levels (Controle+P: 50.01±4.19 µMol/mg ptn; CS: 108.7±7.73 µMol/mg ptn, p<0.001; CS+P: 58.84±3.42 nMol/mg ptn, p<0.01) increased in CS group when compared with other groups. TNF-α expression was observed in CS only. P administration showed an antioxidant action in murine macrophages and reduced cigarette smoke-induced lung inflammation and oxidative stress, probably, by action of its phytochemical compounds actions
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spelling Pôrto, Luís Cristóvão de Moraes Sobrinohttp://lattes.cnpq.br/8153025668900773Souza, Bruna Romana dehttp://lattes.cnpq.br/6955927491661561Bezerra, Frank Silvahttp://lattes.cnpq.br/5194562537283859http://lattes.cnpq.br/7463905179383357Lopes, Alan de Aguiar2021-01-05T18:13:18Z2013-09-202012-07-30LOPES, Alan de Aguiar. Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos. 2012. 130 f. Dissertação (Mestrado em Biologia Humana) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2012.http://www.bdtd.uerj.br/handle/1/7837Chronic obstructive pulmonary disease (DPOC) causes a respiratory capacity reduction and its development is be associated with cigarette smoke. Cigarette has more than 4800 toxic substances in your composition and it causes death of six million people in the world. Studies had been made to find methods to change cigarette-induced health problems. Propolis (P) has been reported as a natural product with several properties. Here, we used two types of experiments, in vitro and in vivo, to study the potential antioxidant use of P. Phytochemical analyze was made to evaluate which compounds are within P. Murine macrophages, RAW 264.7 cell line, are exposed to different concentrations of propolis and following analyses were made: total polyphenols levels; cell viability (MTT); reduction potential (DPPH); total reactive oxygen species levels (ROS) and malondialdehyde (MDA). Thirty C57BL6 mice were divided into 3 groups: Control+P, CS and CS+P. Both CS groups were exposed to 6 cigarettes per day for 5 days. CS group was treated with vehicle. Lung and bronchoalveolar lavage (BAL) were collected for histological analysis and differential cell counts. Analysis for mieloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), oxidized glutathione (GSSG), MDA, nitrite and western blotting for TNF-alpha were performed. Phytochemical analyses of P showed which possesses four main compounds: hydrocinnamic and coumaric acids; artepillin C and drupanin. P showed an increase in total polyphenols (p<0.001), cell viability (p<0.001) and DPPH levels (p<0.001) in concentration-dependent manner, different from MDA (p<0.001) which was inverse pattern. P decreased ROS levels in 15.6 and 31.2 mg/mL groups (p<0.05). Lung histology of Control+P group was similar to CS and CS+P groups, however significant inflammatory cell influx was observed in CS group. Propolis administration reduced significantly macrophages and neutrophils compared with CS group (p<0.01 e p<0.001, respectively). MPO levels was increased in CS (526.5±34.72 mU/mg ptn, p<0.01), but was shown to be reduced in CS+P (385.1±27.64 mU/mg ptn, p<0.05) compared with Control+P (134±12.99 mU/mg ptn, p<0.001), similar pattern was found in antioxidant enzymes: SOD (Controle+P: 523.5±29.6 U/mg ptn; CS: 523.5±29.6 U/mg ptn, p<0.001; CS+P: 246.8±15.69 U/mg ptn, p<0.001), CAT (Controle+P: 37.38±3.39 U/mg ptn; CS: 92.68±6.24 U/mg ptn, p<0.001; CS+P: 59.84±4.55 U/mg ptn, p<0.05) and GPx (Controle+P: 2.23±0.17 (µM/min/mg ptn) x 10-1; CS: 4.51±0.31 (µM/min/mg ptn) x 10-1, p<0.001; CS+P: 2.64±0.19 (µM/min/mg ptn) x 10-1, p<0.05) and different from GSH/GSSG ratio (Controle+P: 1.088±0.17; CS: 0.736±0.07, p<0.05; CS+P: 1.258±0.10, p<0.05). MDA (Controle+P: 0.266±0.05 nMol/mg ptn; CS: 0.94±0.076 nMol/mg ptn, p<0.001; CS+P: 0.498±0.06 nMol/mg ptn, p<0.01) and nitrite levels (Controle+P: 50.01±4.19 µMol/mg ptn; CS: 108.7±7.73 µMol/mg ptn, p<0.001; CS+P: 58.84±3.42 nMol/mg ptn, p<0.01) increased in CS group when compared with other groups. TNF-α expression was observed in CS only. P administration showed an antioxidant action in murine macrophages and reduced cigarette smoke-induced lung inflammation and oxidative stress, probably, by action of its phytochemical compounds actionsA doença pulmonar obstrutiva crônica (DPOC) causa a redução da capacidade respiratória e seu desenvolvimento é associado à fumaça de cigarro. O cigarro possui mais de 4800 substâncias tóxicas e causa a morte de seis milhões de pessoas por ano no mundo. Estudos buscam meios de reverter os males causados pela fumaça de cigarro. A própolis (P) é um produto produzido por abelhas que possui várias propriedades. O objetivo deste trabalho foi avaliar os efeitos antioxidantes da P em macrófagos murinos e na inflamação pulmonar aguda induzida pela fumaça de cigarro (CS) em camundongos. A análise dos compostos fitoquímicos do extrato alcóolico da P (EAP) foi feita por cromatografia gasosa acoplada à espectrometria de massa (GC-MS). Células da linhagem RAW 264.7 foram tratadas em diversas concentrações de P durante 24 horas. Após tratamento, as seguintes análises foram realizadas: polifenóis totais; viabilidade celular (MTT); potencial redutor (DPPH); espécies reativas de oxigênio totais (ROS) e de malondialdeído (MDA). Trinta camundongos C57BL/6 foram divididos em 3 grupos (n=10/grupo): Controle+P, CS e CS+P. Ambos os grupos CS foram expostos a 6 cigarros/dia durante 5 dias. O grupo CS foi tratado com veículo. O pulmão e o lavado broncoalveolar (BAL) foram coletados para análise histológica e contagem diferencial de células. As análises para mieloperoxidase (MPO), superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa reduzida (GSH) e oxidada (GSSG), MDA, nitrito e western blotting para TNF-alfa foram realizadas. A análise fitoquímica do EAP mostrou a presença dos ácidos hidrocinâmicos e coumárico, a artepilina C e a drupanina. Foi observado o aumento concentração-dependente dos níveis de polifenóis totais (p<0,001), do MTT (p<0,001) e do DPPH (p<0,001), e o inverso com o MDA (p<0,001). Os níveis de ROS diminuem nas concentrações de 15,6 e 31,2 mg/mL (p<0,05, ambos). A histologia pulmonar do grupo Controle+P foi similar ao do CS+P e foi observado um influxo de macrófagos e neutrófilos no grupo CS (p<0,01 e p<0,001, respectivamente). Os níveis de MPO foram aumentados no grupo CS (526,5±34,72 mU/mg ptn, p<0,01), mas houve uma redução no grupo CS+P (385,1±27,64 mU/mg ptn, p<0,05) comparável ao Controle+P (134±12,99 mU/mg ptn, p<0,001), o mesmo aconteceu com as enzimas antioxidantes: SOD (Controle+P: 523,5±29,6 U/mg ptn; CS: 523,5±29,6 U/mg ptn, p<0,001; CS+P: 246,8±15,69 U/mg ptn, p<0,001); CAT (Controle+P: 37,38±3,39 U/mg ptn; CS: 92,68±6,24 U/mg ptn, p<0,001; CS+P: 59,84±4,55 U/mg ptn, p<0,05); GPx (Controle+P: 2,23±0,17 (µM/min/mg ptn) x 10-1; CS: 4,51±0,31 (µM/min/mg ptn) x 10-1, p<0,001; CS+P: 2,64±0,19 (µM/min/mg ptn) x 10-1, p<0,05). O inverso ocorreu com a relação GSH/GSSG (Controle+P: 1,088±0,17; CS: 0,736±0,07, p<0,05; CS+P: 1,258±0,10, p<0,05). Os níveis de MDA (Controle+P: 0,266±0,05 nMol/mg ptn; CS: 0,94±0,076 nMol/mg ptn, p<0,001; CS+P: 0,498±0,06 nMol/mg ptn, p<0,01) e de nitrito (Controle+P: 50,01±4,19 µMol/mg ptn; CS: 108,7±7,73 µMol/mg ptn, p<0,001; CS+P: 58,84±3,42 nMol/mg ptn, p<0,01) estavam aumentados no CS que em outros grupos. A expressão de TNF-α foi observada no grupo CS. O tratamento da P apresentou ação anti-inflamatória e antioxidante em macrófagos e em camundongos expostos à fumaça de cigarro, possivelmente pela ação dos polifenóis presentes nelaSubmitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:13:18Z No. of bitstreams: 3 Pre.pdf: 318058 bytes, checksum: 01403f0170a12798cb9246243f464696 (MD5) Textual.pdf: 1147038 bytes, checksum: ef0a37ad149a46f862db2007938edef8 (MD5) Apendices.pdf: 12314884 bytes, checksum: 6487de42a57db7847b4ab5ff3bdd2828 (MD5)Made available in DSpace on 2021-01-05T18:13:18Z (GMT). No. of bitstreams: 3 Pre.pdf: 318058 bytes, checksum: 01403f0170a12798cb9246243f464696 (MD5) Textual.pdf: 1147038 bytes, checksum: ef0a37ad149a46f862db2007938edef8 (MD5) Apendices.pdf: 12314884 bytes, checksum: 6487de42a57db7847b4ab5ff3bdd2828 (MD5) Previous issue date: 2012-07-30Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Biologia Humana e ExperimentalUERJBRCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesPropolisMurine macrophagesCigarette smokeInflammationOxidative stressLungPrópolisMacrófagos murinosPulmãoFumaça de cigarroAntioxidanteAnti-inflamatórioCNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIAEstudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongosAnalysis of antioxidant and anti-inflammatory effects of propolis in RAW 264.7 cells and acute lung inflammation in mouse cigarette smoke-exposedinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALPre.pdfapplication/pdf318058http://www.bdtd.uerj.br/bitstream/1/7837/1/Pre.pdf01403f0170a12798cb9246243f464696MD51Textual.pdfapplication/pdf1147038http://www.bdtd.uerj.br/bitstream/1/7837/2/Textual.pdfef0a37ad149a46f862db2007938edef8MD52Apendices.pdfapplication/pdf12314884http://www.bdtd.uerj.br/bitstream/1/7837/3/Apendices.pdf6487de42a57db7847b4ab5ff3bdd2828MD531/78372024-02-26 15:24:07.563oai:www.bdtd.uerj.br:1/7837Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T18:24:07Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
dc.title.alternative.eng.fl_str_mv Analysis of antioxidant and anti-inflammatory effects of propolis in RAW 264.7 cells and acute lung inflammation in mouse cigarette smoke-exposed
title Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
spellingShingle Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
Lopes, Alan de Aguiar
Propolis
Murine macrophages
Cigarette smoke
Inflammation
Oxidative stress
Lung
Própolis
Macrófagos murinos
Pulmão
Fumaça de cigarro
Antioxidante
Anti-inflamatório
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
title_short Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
title_full Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
title_fullStr Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
title_full_unstemmed Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
title_sort Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos
author Lopes, Alan de Aguiar
author_facet Lopes, Alan de Aguiar
author_role author
dc.contributor.advisor1.fl_str_mv Pôrto, Luís Cristóvão de Moraes Sobrino
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8153025668900773
dc.contributor.referee1.fl_str_mv Souza, Bruna Romana de
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/6955927491661561
dc.contributor.referee2.fl_str_mv Bezerra, Frank Silva
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/5194562537283859
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7463905179383357
dc.contributor.author.fl_str_mv Lopes, Alan de Aguiar
contributor_str_mv Pôrto, Luís Cristóvão de Moraes Sobrino
Souza, Bruna Romana de
Bezerra, Frank Silva
dc.subject.eng.fl_str_mv Propolis
Murine macrophages
Cigarette smoke
Inflammation
Oxidative stress
Lung
topic Propolis
Murine macrophages
Cigarette smoke
Inflammation
Oxidative stress
Lung
Própolis
Macrófagos murinos
Pulmão
Fumaça de cigarro
Antioxidante
Anti-inflamatório
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
dc.subject.por.fl_str_mv Própolis
Macrófagos murinos
Pulmão
Fumaça de cigarro
Antioxidante
Anti-inflamatório
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA
description Chronic obstructive pulmonary disease (DPOC) causes a respiratory capacity reduction and its development is be associated with cigarette smoke. Cigarette has more than 4800 toxic substances in your composition and it causes death of six million people in the world. Studies had been made to find methods to change cigarette-induced health problems. Propolis (P) has been reported as a natural product with several properties. Here, we used two types of experiments, in vitro and in vivo, to study the potential antioxidant use of P. Phytochemical analyze was made to evaluate which compounds are within P. Murine macrophages, RAW 264.7 cell line, are exposed to different concentrations of propolis and following analyses were made: total polyphenols levels; cell viability (MTT); reduction potential (DPPH); total reactive oxygen species levels (ROS) and malondialdehyde (MDA). Thirty C57BL6 mice were divided into 3 groups: Control+P, CS and CS+P. Both CS groups were exposed to 6 cigarettes per day for 5 days. CS group was treated with vehicle. Lung and bronchoalveolar lavage (BAL) were collected for histological analysis and differential cell counts. Analysis for mieloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), oxidized glutathione (GSSG), MDA, nitrite and western blotting for TNF-alpha were performed. Phytochemical analyses of P showed which possesses four main compounds: hydrocinnamic and coumaric acids; artepillin C and drupanin. P showed an increase in total polyphenols (p<0.001), cell viability (p<0.001) and DPPH levels (p<0.001) in concentration-dependent manner, different from MDA (p<0.001) which was inverse pattern. P decreased ROS levels in 15.6 and 31.2 mg/mL groups (p<0.05). Lung histology of Control+P group was similar to CS and CS+P groups, however significant inflammatory cell influx was observed in CS group. Propolis administration reduced significantly macrophages and neutrophils compared with CS group (p<0.01 e p<0.001, respectively). MPO levels was increased in CS (526.5±34.72 mU/mg ptn, p<0.01), but was shown to be reduced in CS+P (385.1±27.64 mU/mg ptn, p<0.05) compared with Control+P (134±12.99 mU/mg ptn, p<0.001), similar pattern was found in antioxidant enzymes: SOD (Controle+P: 523.5±29.6 U/mg ptn; CS: 523.5±29.6 U/mg ptn, p<0.001; CS+P: 246.8±15.69 U/mg ptn, p<0.001), CAT (Controle+P: 37.38±3.39 U/mg ptn; CS: 92.68±6.24 U/mg ptn, p<0.001; CS+P: 59.84±4.55 U/mg ptn, p<0.05) and GPx (Controle+P: 2.23±0.17 (µM/min/mg ptn) x 10-1; CS: 4.51±0.31 (µM/min/mg ptn) x 10-1, p<0.001; CS+P: 2.64±0.19 (µM/min/mg ptn) x 10-1, p<0.05) and different from GSH/GSSG ratio (Controle+P: 1.088±0.17; CS: 0.736±0.07, p<0.05; CS+P: 1.258±0.10, p<0.05). MDA (Controle+P: 0.266±0.05 nMol/mg ptn; CS: 0.94±0.076 nMol/mg ptn, p<0.001; CS+P: 0.498±0.06 nMol/mg ptn, p<0.01) and nitrite levels (Controle+P: 50.01±4.19 µMol/mg ptn; CS: 108.7±7.73 µMol/mg ptn, p<0.001; CS+P: 58.84±3.42 nMol/mg ptn, p<0.01) increased in CS group when compared with other groups. TNF-α expression was observed in CS only. P administration showed an antioxidant action in murine macrophages and reduced cigarette smoke-induced lung inflammation and oxidative stress, probably, by action of its phytochemical compounds actions
publishDate 2012
dc.date.issued.fl_str_mv 2012-07-30
dc.date.available.fl_str_mv 2013-09-20
dc.date.accessioned.fl_str_mv 2021-01-05T18:13:18Z
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dc.identifier.citation.fl_str_mv LOPES, Alan de Aguiar. Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos. 2012. 130 f. Dissertação (Mestrado em Biologia Humana) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2012.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/7837
identifier_str_mv LOPES, Alan de Aguiar. Estudos dos efeitos antioxidantes e anti-inflamatórios da própolis sobre as células RAW 264.7 e na resposta inflamatória pulmonar aguda causada pela exposição à fumaça de cigarro em camundongos. 2012. 130 f. Dissertação (Mestrado em Biologia Humana) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2012.
url http://www.bdtd.uerj.br/handle/1/7837
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dc.publisher.initials.fl_str_mv UERJ
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
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