Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo

Detalhes bibliográficos
Autor(a) principal: Cichota, Luiz Carlos
Data de Publicação: 2016
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
dARK ID: ark:/26339/001300000knz0
Texto Completo: http://repositorio.ufsm.br/handle/1/18131
Resumo: Chronic kidney disease (CKD) is a condition in which the kidneys lose their ability to perform basic functions. Hemodialysis is the most commonly used alternative treatment for these patients, however, it exposes these individuals to oxidative stress, which is an importante risk factor for DNA damage. The decrease in functional capacity of the kidneys can trigger serious health problems for these patients, such as anemia, which has significant impact on their quality of life and needs to be corrected with adjuvant therapy, primarily intravenous iron. However, iron is an oxidative metal that enhances the oxidative stress, which may result in an increase in DNA damage. Thus the aim of the study was to investigate the association between iron metabolism, oxidative stress and free circulating DNA in patients with renal disease undergoing hemodialysis. Iron levels, ferritin, transferrin, total antioxidant capacity (TAC), the total oxidant status (TOS) and Albumin modified by ischemia (AMI) and damage DNA in the test Picogreen® were measured in forty CKD patients undergoing hemodialysis and forty control subjects. We observed that the DNA damage was significantly elevated in patients with CKD undergoing hemodialysis when compared to the control group. Furthermore, we demonstrated an association between the increase in DNA damage in the CKD with serum ferritin levels and decreased glomerular filtration rate (GFR). We also noticed that a single hemodialysis session did not increased DNA damage. Moreover, this study also found out that patients with CKD undergoing hemodialysis who used intravenous iron therapy had higher circulating free DNA levels than those who did not use therapy with iron. In this study, we also observed that patients who used intravenous iron therapy had a decrease in antioxidant levels (TAC) and a significant increase in oxidant levels (TOS and IMA). Thus, we speculate that the events that affect patients with CKD, such as an increase in the stock of iron, declining renal function, oxidative imbalance and treatment with intravenous iron may be factors that directly contribute to increased DNA damage.
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spelling Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativoAssessment of DNA damage in patients with chronic kidney disease undergoing hemodialysis and its association with iron metabolism and oxidative stressDoença renal crônicaHemodiáliseDano ao DNAFerritinaEstresse oxidativoFerroChronic kidney diseaseHemodialysisDNA damageIronFerritinOxidative stressCNPQ::CIENCIAS DA SAUDE::FARMACIAChronic kidney disease (CKD) is a condition in which the kidneys lose their ability to perform basic functions. Hemodialysis is the most commonly used alternative treatment for these patients, however, it exposes these individuals to oxidative stress, which is an importante risk factor for DNA damage. The decrease in functional capacity of the kidneys can trigger serious health problems for these patients, such as anemia, which has significant impact on their quality of life and needs to be corrected with adjuvant therapy, primarily intravenous iron. However, iron is an oxidative metal that enhances the oxidative stress, which may result in an increase in DNA damage. Thus the aim of the study was to investigate the association between iron metabolism, oxidative stress and free circulating DNA in patients with renal disease undergoing hemodialysis. Iron levels, ferritin, transferrin, total antioxidant capacity (TAC), the total oxidant status (TOS) and Albumin modified by ischemia (AMI) and damage DNA in the test Picogreen® were measured in forty CKD patients undergoing hemodialysis and forty control subjects. We observed that the DNA damage was significantly elevated in patients with CKD undergoing hemodialysis when compared to the control group. Furthermore, we demonstrated an association between the increase in DNA damage in the CKD with serum ferritin levels and decreased glomerular filtration rate (GFR). We also noticed that a single hemodialysis session did not increased DNA damage. Moreover, this study also found out that patients with CKD undergoing hemodialysis who used intravenous iron therapy had higher circulating free DNA levels than those who did not use therapy with iron. In this study, we also observed that patients who used intravenous iron therapy had a decrease in antioxidant levels (TAC) and a significant increase in oxidant levels (TOS and IMA). Thus, we speculate that the events that affect patients with CKD, such as an increase in the stock of iron, declining renal function, oxidative imbalance and treatment with intravenous iron may be factors that directly contribute to increased DNA damage.A doença renal crônica (DRC) é a condição na qual os rins perdem a capacidade de efetuar funções básicas. A hemodiálise é o tratamento alternativo mais utilizado para esses pacientes, porém esse tratamento expõe tais indivíduos ao estresse oxidativo, o qual constitui importante fator de risco para lesão no DNA. A diminuição da capacidade funcional dos rins pode desencadear sérios problemas de saúde para esses pacientes, como a anemia, a qual possui significativo impacto sobre a qualidade de vida dos mesmos, necessitando ser corrigida com terapias adjuvantes, principalmente de ferro intravenoso. No entanto, o ferro é um metal oxidativo que potencializa o estresse oxidativo, podendo resultar em um aumento no dano ao DNA. Assim, o objetivo do estudo foi investigar a associação entre o metabolismo do ferro, estresse oxidativo e DNA livre circulante em pacientes com doença renal e submetidos à hemodiálise. Foram mensurados ferro, ferritina, transferrina, capacidade antioxidante total (TAC), estado oxidante total (TOS) e albumina modificada pela isquemia (IMA), bem como lesão no DNA pelo ensaio Picogreen® em quarenta pacientes com DRC submetidos à hemodiálise e quarenta indivíduos controle. Observou-se que o dano no DNA foi significativamente elevado nos pacientes com DRC submetidos à hemodiálise, quando comparado com o grupo controle. Além disso, foi demonstrada uma associação entre o aumento do dano ao DNA na DRC com os níveis séricos de ferritina e decréscimo da taxa de filtração glomerular (TFG). Constatou-se, também, que uma única sessão de hemodiálise não promoveu aumento do dano ao DNA. Além disso, foi verificado que os pacientes com DRC submetidos à hemodiálise e que utilizavam terapia com ferro intravenoso obtiveram maiores níveis de DNA livre circulante em relação aos que não utlizavam esta terapia. Neste estudo, observou-se, ainda, que os pacientes que utilizavam a terapia com ferro intravenoso apresentaram uma diminuição dos níveis de antioxidantes (TAC) e um aumento significativo dos níveis de oxidantes (TOS e IMA). Desta forma, consideramos que os eventos que acometem os pacientes com DRC, tais como aumento do estoque de ferro, declínio da função renal, desequilíbrio oxidativo, bem como o tratamento com ferro intravenoso, podem ser fatores que contribuem diretamente para o aumento do dano ao DNA.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeMoresco, Rafael Noalhttp://lattes.cnpq.br/2269922709577261Silva, Jose Edson Paz dahttp://lattes.cnpq.br/1177504021154172Bauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Duarte, Marta Maria Medeiros Frescurahttp://lattes.cnpq.br/6277584896102052Sagrillo, Michele Roratohttp://lattes.cnpq.br/2566285176244747Cichota, Luiz Carlos2019-09-03T21:55:07Z2019-09-03T21:55:07Z2016-06-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18131ark:/26339/001300000knz0porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-09-04T06:02:17Zoai:repositorio.ufsm.br:1/18131Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-09-04T06:02:17Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
Assessment of DNA damage in patients with chronic kidney disease undergoing hemodialysis and its association with iron metabolism and oxidative stress
title Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
spellingShingle Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
Cichota, Luiz Carlos
Doença renal crônica
Hemodiálise
Dano ao DNA
Ferritina
Estresse oxidativo
Ferro
Chronic kidney disease
Hemodialysis
DNA damage
Iron
Ferritin
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
title_full Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
title_fullStr Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
title_full_unstemmed Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
title_sort Avaliação do dano ao DNA em pacientes com doença renal crônica submetidos à hemodiálise e sua associação com o metabolismo do ferro e estresse oxidativo
author Cichota, Luiz Carlos
author_facet Cichota, Luiz Carlos
author_role author
dc.contributor.none.fl_str_mv Moresco, Rafael Noal
http://lattes.cnpq.br/2269922709577261
Silva, Jose Edson Paz da
http://lattes.cnpq.br/1177504021154172
Bauermann, Liliane de Freitas
http://lattes.cnpq.br/5849925846135968
Duarte, Marta Maria Medeiros Frescura
http://lattes.cnpq.br/6277584896102052
Sagrillo, Michele Rorato
http://lattes.cnpq.br/2566285176244747
dc.contributor.author.fl_str_mv Cichota, Luiz Carlos
dc.subject.por.fl_str_mv Doença renal crônica
Hemodiálise
Dano ao DNA
Ferritina
Estresse oxidativo
Ferro
Chronic kidney disease
Hemodialysis
DNA damage
Iron
Ferritin
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Doença renal crônica
Hemodiálise
Dano ao DNA
Ferritina
Estresse oxidativo
Ferro
Chronic kidney disease
Hemodialysis
DNA damage
Iron
Ferritin
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Chronic kidney disease (CKD) is a condition in which the kidneys lose their ability to perform basic functions. Hemodialysis is the most commonly used alternative treatment for these patients, however, it exposes these individuals to oxidative stress, which is an importante risk factor for DNA damage. The decrease in functional capacity of the kidneys can trigger serious health problems for these patients, such as anemia, which has significant impact on their quality of life and needs to be corrected with adjuvant therapy, primarily intravenous iron. However, iron is an oxidative metal that enhances the oxidative stress, which may result in an increase in DNA damage. Thus the aim of the study was to investigate the association between iron metabolism, oxidative stress and free circulating DNA in patients with renal disease undergoing hemodialysis. Iron levels, ferritin, transferrin, total antioxidant capacity (TAC), the total oxidant status (TOS) and Albumin modified by ischemia (AMI) and damage DNA in the test Picogreen® were measured in forty CKD patients undergoing hemodialysis and forty control subjects. We observed that the DNA damage was significantly elevated in patients with CKD undergoing hemodialysis when compared to the control group. Furthermore, we demonstrated an association between the increase in DNA damage in the CKD with serum ferritin levels and decreased glomerular filtration rate (GFR). We also noticed that a single hemodialysis session did not increased DNA damage. Moreover, this study also found out that patients with CKD undergoing hemodialysis who used intravenous iron therapy had higher circulating free DNA levels than those who did not use therapy with iron. In this study, we also observed that patients who used intravenous iron therapy had a decrease in antioxidant levels (TAC) and a significant increase in oxidant levels (TOS and IMA). Thus, we speculate that the events that affect patients with CKD, such as an increase in the stock of iron, declining renal function, oxidative imbalance and treatment with intravenous iron may be factors that directly contribute to increased DNA damage.
publishDate 2016
dc.date.none.fl_str_mv 2016-06-14
2019-09-03T21:55:07Z
2019-09-03T21:55:07Z
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 http://repositorio.ufsm.br/handle/1/18131
dc.identifier.dark.fl_str_mv ark:/26339/001300000knz0
url http://repositorio.ufsm.br/handle/1/18131
identifier_str_mv ark:/26339/001300000knz0
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
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 Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Ciências Farmacêuticas
Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Ciências Farmacêuticas
Centro de Ciências da Saúde
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
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