DNA damage in homocystinuria: 8-oxo-, 8-dihydro-2'-deoxyguanosine levels in cystathionine-ß-synthase deficient patients and the in vitro protective effect of N-acetylLcysteine
Clin. biomed. res
; 38(1): 50-57, 2018.
Article
em En
| LILACS
| ID: biblio-994866
Biblioteca responsável:
BR18.1
ABSTRACT
Introduction:
Homocysteine (Hcy) tissue accumulation occurs in a metabolic disease characterized biochemically by cystathionine ß-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 CBSdeficient 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Acetilcisteína
/
Dano ao DNA
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Estresse Oxidativo
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Cistationina
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Desoxiguanosina
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Homocistinúria
/
Antioxidantes
Tipo de estudo:
Observational_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
Idioma:
En
Revista:
Clin. biomed. res
Assunto da revista:
MEDICINA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Brasil