Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical

Detalhes bibliográficos
Ano de defesa: 2008
Autor(a) principal: Maldonado, Paula Acosta
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
dARK ID: ark:/26339/001300000gzf9
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
ADA
Link de acesso: http://repositorio.ufsm.br/handle/1/4403
Resumo: Uterine cancers are considered to be one of the most important malignant diseases of the female genital tract, preceded only by breast cancer. The tumor cells may produce oxidative disturbances as well as damage to the antioxidant system. Cancer may also induce alterations in blood coagulation, ranging anywhere from slight platelet activation to thrombus formation, which impair the quality of life of these patients. This study aimed to evaluate the influence of uterine cervix cancer and its treatments, such as conization and radiotherapy (RTX), on the possible development of thrombogenic processes, on the oxidative profile and on coagulation disorders. Variations in the oxidative profile were analyzed through the determination of parameters such as TBARS and protein carbonyl content and antioxidant defenses were determined from the activity of catalase and reduced glutathione (GSH). Thromboembolic disorders were evaluated by the activity of enzymes such as NTPDase, E-NPP and 5 -nucleotidase, since all of these are present in the platelet membrane, as well as the activity of ADA which has an important role in the degradation of adenosine, which in turn is known for possessing tumor promoting functions. The evaluation of oxidative and antioxidant parameters revealed that TBARS levels, protein carbonyl, GSH and the activity of catalase were enhanced in the non treated group when compared to the other groups. The increased levels of oxidants may reflect their enhanced production by tumor cells, since it is known that antioxidant levels are enhanced at the beginning of the neoplasic transformation in an attempt to neutralize the enhanced free radical production. As for the enzymes involved in the thrombogenic process, the results revealed a significant inhibition of NTPDase in groups treated for a long time ago by CNZ or RTX, when compared to the more recently treated groups and the control. The reduced ATP hydrolysis could be acting to prevent ADP formation, since this nucleotide is the main agent that promotes platelet aggregation. The reduced AMP hydrolysis in all the treated groups, may be a result of the reduced production of adenosine due to the effectiveness of the treatments. In the conization and RTX treated groups, E-NPP activity, both in serum and platelets, was reduced when compared to the control and non treated groups, which could be a reflection of reduced nucleotide degradation, due to the absence of tumor cells and, in turn, lower production of adenosine, which is a tumor promoting agent and is also the substrate for ADA. The probable absence of tumor cells due to the effectiveness of the treatments and the reduced adenosine concentration may be responsible for the reduced ADA activity found in the same groups. The inhibition of enzymes such as E-NPP, 5 -nucleotidase and ADA in all the treated groups may suggest the role of these enzymes in sequentially controlling the concentrations of nucleotides in the extracellular environment. NTPDase appears to be more sensitive to changes caused by the passing of time after the end of the treatments. We may say that the surgery itself causes greater alterations in enzymes such as E-NPP, 5 -nucleotidase and ADA from platelets, because in the groups recently treated by CNZ these activities were enhanced as compared with the group recently treated by RTX, possibly as a result of platelet alteration, which would be responsible for the enzymatic alterations observed. NTPDase is more involved in the control of platelet aggregation and the enzymes 5`-nucleotidase, E-NPP and ADA are more involved in controlling adenosine concentrations.
id UFSM_dd968eabc5b963b6a0cbdd1bf592dc43
oai_identifier_str oai:repositorio.ufsm.br:1/4403
network_acronym_str UFSM
network_name_str Manancial - Repositório Digital da UFSM
repository_id_str
spelling Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervicalEvaluation of oxidative stress profile and activity of ecto-enzymes in patients with cervical intraepithelial neoplasiaCâncer de úteroRadioterapiaConizaçãoEstresse oxidativoPlaquetasTromboseNTPDaseE-NPPADAUterine cancerRadiotherapyConizationOxidative stressPlateletsThrombosisNTPDaseE-NPPADACNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAUterine cancers are considered to be one of the most important malignant diseases of the female genital tract, preceded only by breast cancer. The tumor cells may produce oxidative disturbances as well as damage to the antioxidant system. Cancer may also induce alterations in blood coagulation, ranging anywhere from slight platelet activation to thrombus formation, which impair the quality of life of these patients. This study aimed to evaluate the influence of uterine cervix cancer and its treatments, such as conization and radiotherapy (RTX), on the possible development of thrombogenic processes, on the oxidative profile and on coagulation disorders. Variations in the oxidative profile were analyzed through the determination of parameters such as TBARS and protein carbonyl content and antioxidant defenses were determined from the activity of catalase and reduced glutathione (GSH). Thromboembolic disorders were evaluated by the activity of enzymes such as NTPDase, E-NPP and 5 -nucleotidase, since all of these are present in the platelet membrane, as well as the activity of ADA which has an important role in the degradation of adenosine, which in turn is known for possessing tumor promoting functions. The evaluation of oxidative and antioxidant parameters revealed that TBARS levels, protein carbonyl, GSH and the activity of catalase were enhanced in the non treated group when compared to the other groups. The increased levels of oxidants may reflect their enhanced production by tumor cells, since it is known that antioxidant levels are enhanced at the beginning of the neoplasic transformation in an attempt to neutralize the enhanced free radical production. As for the enzymes involved in the thrombogenic process, the results revealed a significant inhibition of NTPDase in groups treated for a long time ago by CNZ or RTX, when compared to the more recently treated groups and the control. The reduced ATP hydrolysis could be acting to prevent ADP formation, since this nucleotide is the main agent that promotes platelet aggregation. The reduced AMP hydrolysis in all the treated groups, may be a result of the reduced production of adenosine due to the effectiveness of the treatments. In the conization and RTX treated groups, E-NPP activity, both in serum and platelets, was reduced when compared to the control and non treated groups, which could be a reflection of reduced nucleotide degradation, due to the absence of tumor cells and, in turn, lower production of adenosine, which is a tumor promoting agent and is also the substrate for ADA. The probable absence of tumor cells due to the effectiveness of the treatments and the reduced adenosine concentration may be responsible for the reduced ADA activity found in the same groups. The inhibition of enzymes such as E-NPP, 5 -nucleotidase and ADA in all the treated groups may suggest the role of these enzymes in sequentially controlling the concentrations of nucleotides in the extracellular environment. NTPDase appears to be more sensitive to changes caused by the passing of time after the end of the treatments. We may say that the surgery itself causes greater alterations in enzymes such as E-NPP, 5 -nucleotidase and ADA from platelets, because in the groups recently treated by CNZ these activities were enhanced as compared with the group recently treated by RTX, possibly as a result of platelet alteration, which would be responsible for the enzymatic alterations observed. NTPDase is more involved in the control of platelet aggregation and the enzymes 5`-nucleotidase, E-NPP and ADA are more involved in controlling adenosine concentrations.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOs carcinomas uterinos despontam como uma das doenças malignas mais importantes do trato genital feminino, precedido apenas pelo câncer de mama. As células tumorais podem originar distúrbios oxidativos, bem como prejuízo das defesas antioxidantes desses pacientes. O câncer também pode induzir alterações na coagulação sangüínea que vão desde uma pequena ativação plaquetária até a formação de trombos na circulação, os quais prejudicam a qualidade de vida desses pacientes. Este trabalho teve como objetivo avaliar a influência do carcinoma cervical uterino e de tratamentos como a conização (CNZ) e a radioterapia (RTX) sobre o possível desenvolvimento de processos trombogênicos, sobre o perfil oxidativo e sobre os distúrbios da coagulação. As variações no perfil oxidativo foram analisadas pela determinação de parâmetros como o conteúdo de TBARS e de proteína carbonil, e as defesas antioxidantes através da atividade da enzima catalase e dos níveis de glutationa reduzida (GSH). As desordens tromboembólicas foram analisadas pela determinação da atividade de enzimas como a NTPDase, a E-NPP e a 5 -nucleotidase, enzimas presentes na membrana plaquetária, bem como através da atividade da enzima ADA a qual tem a importante função na degradação da adenosina, que reconhecidamente desempenha funções promotoras de tumor. A avaliação dos parâmetros oxidativos e antioxidantes revelou que os níveis de TBARS, de proteína carbonil, de GSH e a atividade da enzima catalase estavam aumentados no grupo de pacientes não tratados em relação aos demais grupos. O aumentado nível de oxidantes pode ser reflexo de um aumento na sua produção pela célula tumoral. Os antioxidantes podem estar aumentados possivelmente por estar no início da transformação neoplásica tumoral na tentativa de compensar o aumento da produção de espécies reativas. Com relação às enzimas envolvidas nos processos tromboembólicos, os resultados revelaram que ocorreu uma inibição significativa da enzima NTPDase nos grupos tratados há mais tempo tanto por CNZ quanto por RTX, em relação aos grupos tratados recentemente e em relação ao grupo controle. A reduzida hidrólise do ATP poderia estar atuando como forma de prevenção contra a formação do ADP, visto que este nucleotídeo é o principal agente promotor da agregação plaquetária. No caso da enzima 5 -nucleotidase observamos uma reduzida hidrólise do AMP, em todos os grupos tratados, que pode ser o resultado da reduzida produção de adenosina pela efetividade dos tratamentos. Em todos os grupos tratados por CNZ e RTX a atividade da E-NPP, tanto em soro quanto em plaquetas, estava reduzida em relação ao grupo controle e ao grupo com neoplasia não-tratada, podendo ser o reflexo da reduzida degradação de nucleotídeos, pela ausência das células tumorais, formando menos adenosina, a qual é um agente promotor de tumor e também o substrato para a ADA. A ausência de células tumorais pela efetividade dos tratamentos e a reduzida concentração de adenosina, pode ser responsável pela reduzida atividade da ADA nos mesmos grupos. A inibição da atividade das enzimas E-NPP, 5 -nucleotidase e da ADA nos grupos tratados, pode sugerir o papel dessas enzimas no controle seqüencial das concentrações de nucleotídeos no meio extracelular. A enzima NTPDase parece ser um pouco mais sensível às mudanças provocadas pelo tempo transcorrido após o término dos tratamentos. Pode-se inferir também, que a cirurgia causa maiores alterações nas enzimas E-NPP, 5 -nucleotidase e ADA de plaquetas, pelo fato de que nos grupos tratados recentemente por CNZ estas atividades encontram-se aumentadas em relação grupo tratado recentemente por RTX. Sugere-se, com esses resultados, que há uma possível alteração nas plaquetas, causada pelo processo cirúrgico, o qual seria o responsável pelas modificações enzimáticas observadas e que os tratamentos foram efetivos em combater as células tumorais uma vez que, de uma maneira geral há uma inibição das atividades das enzimas em questão, e também devido ao fato de que os testes de coagulação, possíveis indicadores de trombose associada ao câncer, não demonstraram-se alterados. Corroborando estes achados os exames citopatológicos apresentaram alterações celulares compatíveis com a normalidade. A enzima NTPDase demonstra-se estar envolvida no controle da agregação plaquetária e as enzimas 5`-nucleotidase, E-NPP e ADA parecem estar mais envolvidas no controle dos níveis de adenosina. Palavras-chave: Câncer de útero, radioterapia, conização, estresse oxidativo, plaquetas, trombose, NTPDase, E-NPP, ADA.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaSchetinger, Maria Rosa ChitolinaNogueira, Cristina Waynehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9Bogo, Mauricio Reishttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782767J9Rubin, Maribel Antonellohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7Burger, Marilise Escobarhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6Maldonado, Paula Acosta2017-04-262017-04-262008-08-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfMALDONADO, Paula Acosta. Evaluation of oxidative stress profile and activity of ecto-enzymes in patients with cervical intraepithelial neoplasia. 2008. 110 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008.http://repositorio.ufsm.br/handle/1/4403ark:/26339/001300000gzf9porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2017-07-25T14:06:35Zoai:repositorio.ufsm.br:1/4403Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/PUBhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.com||manancial@ufsm.bropendoar:2017-07-25T14:06:35Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
Evaluation of oxidative stress profile and activity of ecto-enzymes in patients with cervical intraepithelial neoplasia
title Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
spellingShingle Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
Maldonado, Paula Acosta
Câncer de útero
Radioterapia
Conização
Estresse oxidativo
Plaquetas
Trombose
NTPDase
E-NPP
ADA
Uterine cancer
Radiotherapy
Conization
Oxidative stress
Platelets
Thrombosis
NTPDase
E-NPP
ADA
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
title_full Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
title_fullStr Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
title_full_unstemmed Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
title_sort Avaliação do perfil oxidativo e da atividade de ectoenzimas em pacientes com neoplasia intra-epitelial cervical
author Maldonado, Paula Acosta
author_facet Maldonado, Paula Acosta
author_role author
dc.contributor.none.fl_str_mv Schetinger, Maria Rosa Chitolina
Nogueira, Cristina Wayne
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9
Bogo, Mauricio Reis
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782767J9
Rubin, Maribel Antonello
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7
Burger, Marilise Escobar
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6
dc.contributor.author.fl_str_mv Maldonado, Paula Acosta
dc.subject.por.fl_str_mv Câncer de útero
Radioterapia
Conização
Estresse oxidativo
Plaquetas
Trombose
NTPDase
E-NPP
ADA
Uterine cancer
Radiotherapy
Conization
Oxidative stress
Platelets
Thrombosis
NTPDase
E-NPP
ADA
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic Câncer de útero
Radioterapia
Conização
Estresse oxidativo
Plaquetas
Trombose
NTPDase
E-NPP
ADA
Uterine cancer
Radiotherapy
Conization
Oxidative stress
Platelets
Thrombosis
NTPDase
E-NPP
ADA
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Uterine cancers are considered to be one of the most important malignant diseases of the female genital tract, preceded only by breast cancer. The tumor cells may produce oxidative disturbances as well as damage to the antioxidant system. Cancer may also induce alterations in blood coagulation, ranging anywhere from slight platelet activation to thrombus formation, which impair the quality of life of these patients. This study aimed to evaluate the influence of uterine cervix cancer and its treatments, such as conization and radiotherapy (RTX), on the possible development of thrombogenic processes, on the oxidative profile and on coagulation disorders. Variations in the oxidative profile were analyzed through the determination of parameters such as TBARS and protein carbonyl content and antioxidant defenses were determined from the activity of catalase and reduced glutathione (GSH). Thromboembolic disorders were evaluated by the activity of enzymes such as NTPDase, E-NPP and 5 -nucleotidase, since all of these are present in the platelet membrane, as well as the activity of ADA which has an important role in the degradation of adenosine, which in turn is known for possessing tumor promoting functions. The evaluation of oxidative and antioxidant parameters revealed that TBARS levels, protein carbonyl, GSH and the activity of catalase were enhanced in the non treated group when compared to the other groups. The increased levels of oxidants may reflect their enhanced production by tumor cells, since it is known that antioxidant levels are enhanced at the beginning of the neoplasic transformation in an attempt to neutralize the enhanced free radical production. As for the enzymes involved in the thrombogenic process, the results revealed a significant inhibition of NTPDase in groups treated for a long time ago by CNZ or RTX, when compared to the more recently treated groups and the control. The reduced ATP hydrolysis could be acting to prevent ADP formation, since this nucleotide is the main agent that promotes platelet aggregation. The reduced AMP hydrolysis in all the treated groups, may be a result of the reduced production of adenosine due to the effectiveness of the treatments. In the conization and RTX treated groups, E-NPP activity, both in serum and platelets, was reduced when compared to the control and non treated groups, which could be a reflection of reduced nucleotide degradation, due to the absence of tumor cells and, in turn, lower production of adenosine, which is a tumor promoting agent and is also the substrate for ADA. The probable absence of tumor cells due to the effectiveness of the treatments and the reduced adenosine concentration may be responsible for the reduced ADA activity found in the same groups. The inhibition of enzymes such as E-NPP, 5 -nucleotidase and ADA in all the treated groups may suggest the role of these enzymes in sequentially controlling the concentrations of nucleotides in the extracellular environment. NTPDase appears to be more sensitive to changes caused by the passing of time after the end of the treatments. We may say that the surgery itself causes greater alterations in enzymes such as E-NPP, 5 -nucleotidase and ADA from platelets, because in the groups recently treated by CNZ these activities were enhanced as compared with the group recently treated by RTX, possibly as a result of platelet alteration, which would be responsible for the enzymatic alterations observed. NTPDase is more involved in the control of platelet aggregation and the enzymes 5`-nucleotidase, E-NPP and ADA are more involved in controlling adenosine concentrations.
publishDate 2008
dc.date.none.fl_str_mv 2008-08-22
2017-04-26
2017-04-26
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.uri.fl_str_mv MALDONADO, Paula Acosta. Evaluation of oxidative stress profile and activity of ecto-enzymes in patients with cervical intraepithelial neoplasia. 2008. 110 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008.
http://repositorio.ufsm.br/handle/1/4403
dc.identifier.dark.fl_str_mv ark:/26339/001300000gzf9
identifier_str_mv MALDONADO, Paula Acosta. Evaluation of oxidative stress profile and activity of ecto-enzymes in patients with cervical intraepithelial neoplasia. 2008. 110 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008.
ark:/26339/001300000gzf9
url http://repositorio.ufsm.br/handle/1/4403
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com||manancial@ufsm.br
_version_ 1847153400585650176