Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20

Detalhes bibliográficos
Autor(a) principal: Fraga, Carolina Miguel
Data de Publicação: 2015
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFG
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/10477
Resumo: Human infections caused by Taenia spp may be more frequent than they are reported especially if occurred in immunodepressed patients and if the location of the parasites does not involve vital organs. Albendazole is one of the drugs used in the treatment of such infections and its use in mass treatment campaigns may accelerate the resistance development from the parasites both in humans and animal hosts. The aim of this study was to in vitro evaluate the biochemical alterations in T. crassiceps cysticerci after the treatment with a benzimidazolic derivatice (RCB20). The cysticerci were removed from the peritoneal cavity of BALB/c mice with 30 days of infection, macroscopically classified and harvested into 6 well culture plates. 30 cysticerci from each development stage in each well received 5mL of supplemented RPMI culture medium which contained sulfoxide albendazole (ABZSO) (6,5 μM or 13 μM), or RCB20 (6,5 μM or 13 μM). After 24h of culture the cysticerci were removed from the culture medium and both were frozen in liquid nitrogen. Liquid chromatography of high performance and spectrophotometric analysis were performed. It was possible to observe a difficulty in the secretion of substances by the treated cysticerci due to differences in the concentrations of the products dosed from the vesicular fluid and from the culture medium. This was an effect from the mode of action of the drugs which affects the tubulin formation. Regarding the glycolysis it was possible to observe a gradation increase in the secretion/excretion (S/E) of lactate in the treated groups while there was a decrease of this organic acid in the vesicular fluid. As to the energetic metabolism and the citric acid cycle it was possible to observe its traditional sense functioning due to the detection of alf- ketoglutarate. It was possible an increase in the concentrations of citrate, malate, fumarate and succinate in the treated groups. The alternative pathway of energy production such as beta-oxidation of fatty acids and protein catabolism were detected with an increase in the metabolites from those pathways in the treated groups. Therefore we conclude that in spite of not blocking the glucose uptake the drugs influenced its uptake which lead to the use of alternative pathways of energy production. In spite of more soluble and stable the RCB20 formulation did not present a different biochemical effect than ABZSO.
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spelling Vinaud, Marina Clarehttp://lattes.cnpq.br/1921551651088660Castro, Ana Maria dehttp://lattes.cnpq.br/9232309971000621Cruz, Aparecido Divino daCosta, Tatiane Luiza daBezerra, José Clecildo BarretoFernandes, Éverton Kort Kamphttp://lattes.cnpq.br/4916519165378614Fraga, Carolina Miguel2020-03-31T11:31:15Z2015-02-23FRAGA, Carolina Miguel. Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20. 2015. 75 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2015.http://repositorio.bc.ufg.br/tede/handle/tede/10477Human infections caused by Taenia spp may be more frequent than they are reported especially if occurred in immunodepressed patients and if the location of the parasites does not involve vital organs. Albendazole is one of the drugs used in the treatment of such infections and its use in mass treatment campaigns may accelerate the resistance development from the parasites both in humans and animal hosts. The aim of this study was to in vitro evaluate the biochemical alterations in T. crassiceps cysticerci after the treatment with a benzimidazolic derivatice (RCB20). The cysticerci were removed from the peritoneal cavity of BALB/c mice with 30 days of infection, macroscopically classified and harvested into 6 well culture plates. 30 cysticerci from each development stage in each well received 5mL of supplemented RPMI culture medium which contained sulfoxide albendazole (ABZSO) (6,5 μM or 13 μM), or RCB20 (6,5 μM or 13 μM). After 24h of culture the cysticerci were removed from the culture medium and both were frozen in liquid nitrogen. Liquid chromatography of high performance and spectrophotometric analysis were performed. It was possible to observe a difficulty in the secretion of substances by the treated cysticerci due to differences in the concentrations of the products dosed from the vesicular fluid and from the culture medium. This was an effect from the mode of action of the drugs which affects the tubulin formation. Regarding the glycolysis it was possible to observe a gradation increase in the secretion/excretion (S/E) of lactate in the treated groups while there was a decrease of this organic acid in the vesicular fluid. As to the energetic metabolism and the citric acid cycle it was possible to observe its traditional sense functioning due to the detection of alf- ketoglutarate. It was possible an increase in the concentrations of citrate, malate, fumarate and succinate in the treated groups. The alternative pathway of energy production such as beta-oxidation of fatty acids and protein catabolism were detected with an increase in the metabolites from those pathways in the treated groups. Therefore we conclude that in spite of not blocking the glucose uptake the drugs influenced its uptake which lead to the use of alternative pathways of energy production. In spite of more soluble and stable the RCB20 formulation did not present a different biochemical effect than ABZSO.Infecções humanas por cisticercos de Taenia spp. podem ser mais frequentes do que são comumente documentadas, especialmente em imunodeprimidos e se a localização dos parasitos não envolver órgãos vitais. O albendazol é um dos fármacos utilizados no tratamento dessas infecções e seu uso em tratamentos em massa pode acelerar o desenvolvimento de resistência, tanto em animais quanto em humanos. O objetivo deste trabalho foi avaliar in vitro as alterações bioquímicas em cisticercos de T. crassiceps, após tratamento com um derivado benzimidazólico, o RCB20. Os cisticercos foram retirados da cavidade peritoneal de camundongos BALB/c fêmeas com 30 dias de infecção, classificados macroscopicamente e semeados em placas de microcultivo de 6 poços. Trinta cisticercos de cada estádio foram colocados em poços acrescido de 5mL de meio RPMI suplementado e acrescido de sulfóxido de albendazol (ABZSO) (6,5 μM e 13 μM) ou RCB20 (6,5 μM e 13 μM). Após 24 horas de cultivo, separou-se os cisticercos do meio de cultura e foram congelados em nitrogênio líquido. Foram realizadas análises em Cromatografia Líquida de Alta Eficiência e espectrofotometria para avaliação do metabolismo energético e respiratório. Observou-se uma dificuldade dos cisticercos em secretar os produtos de seu metabolismo devido a grandes diferenças nas concentrações de metabólitos secretados e detectados no fluido vesicular. Isso ocorreu devido a interferência dos fármacos na formação de tubulinas. Com relação à glicólise observou-se um aumento gradativo na secreção/excreção (S/E) de glicose em ambas concentrações de ABZSO e RCB20 testadas. Observou-se também uma preferência pela via aeróbia de produção de energia devido a não detecção da S/E de lactado nas amostras tratadas com ABZSO e RCB20; enquanto que no conteúdo vesicular observou-se diminuição nas concentrações de lactato. Com relação ao metabolismo energético e ciclo do ácido cítrico, observou-se seu funcionamento no sentido tradicional devido a detecção de alfa-cetoglutarato. Observou-se aumento nas concentrações de citrato, malato, fumarato e succinato nos grupos tratados com ABDZSO e RCB20. As vias alternativas de produção de energia como a beta-oxidação de ácidos graxos e o catabolismo de proteínas foram detectadas, com um aumento da concentração dos metabólitos dessas vias nos grupos tratados. Conclui-se assim, que apesar de não promoverem o bloqueio total na captação de glicose, os ABZSO e o RCB20 influenciaram em sua captação, induzindo o parasito a utilizar vias alternativas de produção de energia, com as vias de oxidação de ácidos graxos e de degradação de proteínas. Além disso, apesar de mais solúvel e estável o RCB20 não demonstrou atividade bioquímica diferente do ABZSO.Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2020-03-27T20:04:29Z No. of bitstreams: 2 Tese - Carolina Miguel Fraga - 2015.pdf: 10429895 bytes, checksum: 152dc8369ad3b8316d2d4db47308f4f8 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Rejected by Luciana Ferreira (lucgeral@gmail.com), reason: A data da defesa está errada, receio também, o fato de ter colocado em anexo o artigo, pois no Sherpa está O autor não pode arquivar a versão/PDF do editor on 2020-03-30T11:28:16Z (GMT)Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2020-03-30T23:26:38Z No. of bitstreams: 2 Tese - Carolina Miguel Fraga - 2015.pdf: 4883178 bytes, checksum: 464e9e7bbcf02cced381da7ecfa25b2d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2020-03-31T11:31:15Z (GMT) No. of bitstreams: 2 Tese - Carolina Miguel Fraga - 2015.pdf: 4883178 bytes, checksum: 464e9e7bbcf02cced381da7ecfa25b2d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2020-03-31T11:31:15Z (GMT). No. of bitstreams: 2 Tese - Carolina Miguel Fraga - 2015.pdf: 4883178 bytes, checksum: 464e9e7bbcf02cced381da7ecfa25b2d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-02-23Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessTaenia crassicepsMetabolismo energéticoRCB20Sulfóxido de albendazolEnergetic metaolibsmAlbendazole sulfoxideCIENCIAS BIOLOGICAS::PARASITOLOGIAAvaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis6085308344741430434600600600600-7769011444564556288-45445767472715743062075167498588264571reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.eng.fl_str_mv Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
title Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
spellingShingle Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
Fraga, Carolina Miguel
Taenia crassiceps
Metabolismo energético
RCB20
Sulfóxido de albendazol
Energetic metaolibsm
Albendazole sulfoxide
CIENCIAS BIOLOGICAS::PARASITOLOGIA
title_short Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
title_full Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
title_fullStr Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
title_full_unstemmed Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
title_sort Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20
author Fraga, Carolina Miguel
author_facet Fraga, Carolina Miguel
author_role author
dc.contributor.advisor1.fl_str_mv Vinaud, Marina Clare
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1921551651088660
dc.contributor.advisor-co1.fl_str_mv Castro, Ana Maria de
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/9232309971000621
dc.contributor.referee1.fl_str_mv Cruz, Aparecido Divino da
dc.contributor.referee2.fl_str_mv Costa, Tatiane Luiza da
dc.contributor.referee3.fl_str_mv Bezerra, José Clecildo Barreto
dc.contributor.referee4.fl_str_mv Fernandes, Éverton Kort Kamp
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4916519165378614
dc.contributor.author.fl_str_mv Fraga, Carolina Miguel
contributor_str_mv Vinaud, Marina Clare
Castro, Ana Maria de
Cruz, Aparecido Divino da
Costa, Tatiane Luiza da
Bezerra, José Clecildo Barreto
Fernandes, Éverton Kort Kamp
dc.subject.por.fl_str_mv Taenia crassiceps
Metabolismo energético
RCB20
Sulfóxido de albendazol
topic Taenia crassiceps
Metabolismo energético
RCB20
Sulfóxido de albendazol
Energetic metaolibsm
Albendazole sulfoxide
CIENCIAS BIOLOGICAS::PARASITOLOGIA
dc.subject.eng.fl_str_mv Energetic metaolibsm
Albendazole sulfoxide
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::PARASITOLOGIA
description Human infections caused by Taenia spp may be more frequent than they are reported especially if occurred in immunodepressed patients and if the location of the parasites does not involve vital organs. Albendazole is one of the drugs used in the treatment of such infections and its use in mass treatment campaigns may accelerate the resistance development from the parasites both in humans and animal hosts. The aim of this study was to in vitro evaluate the biochemical alterations in T. crassiceps cysticerci after the treatment with a benzimidazolic derivatice (RCB20). The cysticerci were removed from the peritoneal cavity of BALB/c mice with 30 days of infection, macroscopically classified and harvested into 6 well culture plates. 30 cysticerci from each development stage in each well received 5mL of supplemented RPMI culture medium which contained sulfoxide albendazole (ABZSO) (6,5 μM or 13 μM), or RCB20 (6,5 μM or 13 μM). After 24h of culture the cysticerci were removed from the culture medium and both were frozen in liquid nitrogen. Liquid chromatography of high performance and spectrophotometric analysis were performed. It was possible to observe a difficulty in the secretion of substances by the treated cysticerci due to differences in the concentrations of the products dosed from the vesicular fluid and from the culture medium. This was an effect from the mode of action of the drugs which affects the tubulin formation. Regarding the glycolysis it was possible to observe a gradation increase in the secretion/excretion (S/E) of lactate in the treated groups while there was a decrease of this organic acid in the vesicular fluid. As to the energetic metabolism and the citric acid cycle it was possible to observe its traditional sense functioning due to the detection of alf- ketoglutarate. It was possible an increase in the concentrations of citrate, malate, fumarate and succinate in the treated groups. The alternative pathway of energy production such as beta-oxidation of fatty acids and protein catabolism were detected with an increase in the metabolites from those pathways in the treated groups. Therefore we conclude that in spite of not blocking the glucose uptake the drugs influenced its uptake which lead to the use of alternative pathways of energy production. In spite of more soluble and stable the RCB20 formulation did not present a different biochemical effect than ABZSO.
publishDate 2015
dc.date.issued.fl_str_mv 2015-02-23
dc.date.accessioned.fl_str_mv 2020-03-31T11:31:15Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv FRAGA, Carolina Miguel. Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20. 2015. 75 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2015.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/10477
identifier_str_mv FRAGA, Carolina Miguel. Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20. 2015. 75 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2015.
url http://repositorio.bc.ufg.br/tede/handle/tede/10477
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 6085308344741430434
dc.relation.confidence.fl_str_mv 600
600
600
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dc.relation.department.fl_str_mv -7769011444564556288
dc.relation.cnpq.fl_str_mv -4544576747271574306
dc.relation.sponsorship.fl_str_mv 2075167498588264571
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFG
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