DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/174878 |
Resumo: | Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine β-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBS‑deficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2’- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 μM and 200 μM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria. |
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Vanzin, Camila SimioniMescka, Caroline PaulaMarchetti, Desirèe PadilhaDonida, BrunaDeon, MarionJacques, Carlos Eduardo DiazHauschild, Tatiane CristinaFaverzani, Jéssica LambertyHauschild, Tatiane CristinaMoura, Dinara JaquelineSaffi, JeniferCoelho, Daniella de MouraWajner, MoacirWyse, Angela Terezinha de SouzaVargas, Carmen Regla2018-04-20T02:30:40Z20182357-9730http://hdl.handle.net/10183/174878001065410Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine β-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBS‑deficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2’- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 μM and 200 μM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria.application/pdfengClinical and biomedical research. Porto Alegre, RS. Vol. 38, no. 1 (2018), p. 50-57N-Acetil-L-CisteínaHomocistinúriaCystathionine-β-synthase deficiencyOxidative stress8-oxo-77,8-dihydro- 2’-deoxyguanosineHomocysteineDNA damageN-acetyl-L-cysteineDNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteineinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/otherinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001065410.pdf001065410.pdfTexto completo (inglês)application/pdf1066915http://www.lume.ufrgs.br/bitstream/10183/174878/1/001065410.pdf2882d72f66002593a1fccde110ab6bcdMD51TEXT001065410.pdf.txt001065410.pdf.txtExtracted Texttext/plain33494http://www.lume.ufrgs.br/bitstream/10183/174878/2/001065410.pdf.txt970f3de06cdbb04a8ce14057f08ca940MD5210183/1748782020-03-07 04:16:46.069828oai:www.lume.ufrgs.br:10183/174878Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2020-03-07T07:16:46Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
title |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
spellingShingle |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine Vanzin, Camila Simioni N-Acetil-L-Cisteína Homocistinúria Cystathionine-β-synthase deficiency Oxidative stress 8-oxo-7 7,8-dihydro- 2’-deoxyguanosine Homocysteine DNA damage N-acetyl-L-cysteine |
title_short |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
title_full |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
title_fullStr |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
title_full_unstemmed |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
title_sort |
DNA damage in homocystinuria : 8-oxo-, 8-dihydro-2’-deoxyguanosine levels in cystathionine-β-synthase deficient patients and the in vitro protective effect of N-acetyl-L-cysteine |
author |
Vanzin, Camila Simioni |
author_facet |
Vanzin, Camila Simioni Mescka, Caroline Paula Marchetti, Desirèe Padilha Donida, Bruna Deon, Marion Jacques, Carlos Eduardo Diaz Hauschild, Tatiane Cristina Faverzani, Jéssica Lamberty Moura, Dinara Jaqueline Saffi, Jenifer Coelho, Daniella de Moura Wajner, Moacir Wyse, Angela Terezinha de Souza Vargas, Carmen Regla |
author_role |
author |
author2 |
Mescka, Caroline Paula Marchetti, Desirèe Padilha Donida, Bruna Deon, Marion Jacques, Carlos Eduardo Diaz Hauschild, Tatiane Cristina Faverzani, Jéssica Lamberty Moura, Dinara Jaqueline Saffi, Jenifer Coelho, Daniella de Moura Wajner, Moacir Wyse, Angela Terezinha de Souza Vargas, Carmen Regla |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Vanzin, Camila Simioni Mescka, Caroline Paula Marchetti, Desirèe Padilha Donida, Bruna Deon, Marion Jacques, Carlos Eduardo Diaz Hauschild, Tatiane Cristina Faverzani, Jéssica Lamberty Hauschild, Tatiane Cristina Moura, Dinara Jaqueline Saffi, Jenifer Coelho, Daniella de Moura Wajner, Moacir Wyse, Angela Terezinha de Souza Vargas, Carmen Regla |
dc.subject.por.fl_str_mv |
N-Acetil-L-Cisteína Homocistinúria |
topic |
N-Acetil-L-Cisteína Homocistinúria Cystathionine-β-synthase deficiency Oxidative stress 8-oxo-7 7,8-dihydro- 2’-deoxyguanosine Homocysteine DNA damage N-acetyl-L-cysteine |
dc.subject.eng.fl_str_mv |
Cystathionine-β-synthase deficiency Oxidative stress 8-oxo-7 7,8-dihydro- 2’-deoxyguanosine Homocysteine DNA damage N-acetyl-L-cysteine |
description |
Introduction: Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine β-synthase (CBS) deficiency and clinically by mental retardation, vascular problems, and skeletal abnormalities. Previous studies indicate the occurrence of DNA damage secondary to hyperhomocysteinemia and it was observed that DNA damage occurs in leukocytes from CBS-deficient patients. This study aimed to investigate whether an oxidative mechanism could be involved in DNA damage previously found and investigated the in vitro effect of N-acety-L-cysteine (NAC) on DNA damage caused by high Hcy levels. Methods: We evaluated a biomarker of oxidative DNA damage in the urine of CBS‑deficient patients, as well as the in vitro effect of NAC on DNA damage caused by high levels of Hcy. Moreover, a biomarker of lipid oxidative damage was also measured in urine of CBS deficient patients. Results: There was an increase in parameters of DNA (8-oxo-7,8-dihydro-2’- deoxyguanosine) and lipid (15-F2t-isoprostanes levels) oxidative damage in CBS-deficient patients when compared to controls. In addition, a significant positive correlation was found between 15-F2t-isoprostanes levels and total Hcy concentrations. Besides, an in vitro protective effect of NAC at concentrations of 1 and 5 mM was observed on DNA damage caused by Hcy 50 μM and 200 μM. Additionally, we showed a decrease in sulfhydryl content in plasma from CBS-deficient patients when compared to controls. Discussion: These results demonstrated that DNA damage occurs by an oxidative mechanism in CBS deficiency together with lipid oxidative damage, highlighting the NAC beneficial action upon DNA oxidative process, contributing with a new treatment perspective of the patients affected by classic homocystinuria. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-04-20T02:30:40Z |
dc.date.issued.fl_str_mv |
2018 |
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http://hdl.handle.net/10183/174878 |
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2357-9730 |
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001065410 |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Clinical and biomedical research. Porto Alegre, RS. Vol. 38, no. 1 (2018), p. 50-57 |
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