Your browser doesn't support javascript.
loading
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
Vanzin, Camila Simioni; Mescka, Caroline Paula; Donida, Bruna; Marchetti, Desirèe Padilha; Jacques, Carlos Eduardo; Hauschild, Tatiane; Faverzani, Jéssica Lamberty; Deon, Marion; Moura, Dinara Jaqueline; Saffi, Jenifer; Coelho, Daniella de Moura; Wajner, Moacir; Wyse, Angela Terezinha de Souza; Vargas, Carmen Regla.
  • Vanzin, Camila Simioni; Universidade Federal do Rio Grande do Sul. Postgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
  • Mescka, Caroline Paula; Hospital de Clínicas de Porto Alegre. Medical Genetics Service. Porto Alegre. BR
  • Donida, Bruna; Universidade Federal do Rio Grande do Sul. Postgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
  • Marchetti, Desirèe Padilha; Universidade Federal do Rio Grande do Sul. Postgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
  • Jacques, Carlos Eduardo; Universidade Federal do Rio Grande do Sul. Postgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
  • Hauschild, Tatiane; Universidade Federal de Ciências da Saúde de Porto Alegre. Laboratory of Toxicological Genetics. Porto Alegre. BR
  • Faverzani, Jéssica Lamberty; Hospital de Clínicas de Porto Alegre. Medical Genetics Service. Porto Alegre. BR
  • Deon, Marion; Universidade Federal do Rio Grande do Sul. Postgraduate Program in Pharmaceutical Sciences. Porto Alegre. BR
  • Moura, Dinara Jaqueline; Universidade Federal de Ciências da Saúde de Porto Alegre. Laboratory of Toxicological Genetics. Porto Alegre. BR
  • Saffi, Jenifer; Universidade Federal de Ciências da Saúde de Porto Alegre. Laboratory of Toxicological Genetics. Porto Alegre. BR
  • Coelho, Daniella de Moura; Hospital de Clínicas de Porto Alegre. Medical Genetics Service. Porto Alegre. BR
  • Wajner, Moacir; Universidade Federal do Rio Grande do Sul. Posgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
  • Wyse, Angela Terezinha de Souza; Universidade Federal do Rio Grande do Sul. Posgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
  • Vargas, Carmen Regla; Universidade Federal do Rio Grande do Sul. Posgraduate Program in Biological Sciences: Biochemistry. Porto Alegre. BR
Clin. biomed. res ; 38(1): 50-57, 2018.
Article in English | LILACS | ID: biblio-994866
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Acetylcysteine / DNA Damage / Oxidative Stress / Cystathionine / Deoxyguanosine / Homocystinuria / Antioxidants Type of study: Observational study Limits: Adolescent / Adult / Child / Female / Humans Language: English Journal: Clin. biomed. res Journal subject: Medicine Year: 2018 Type: Article Affiliation country: Brazil Institution/Affiliation country: Hospital de Clínicas de Porto Alegre/BR / Universidade Federal de Ciências da Saúde de Porto Alegre/BR / Universidade Federal do Rio Grande do Sul/BR

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Index: LILACS (Americas) Main subject: Acetylcysteine / DNA Damage / Oxidative Stress / Cystathionine / Deoxyguanosine / Homocystinuria / Antioxidants Type of study: Observational study Limits: Adolescent / Adult / Child / Female / Humans Language: English Journal: Clin. biomed. res Journal subject: Medicine Year: 2018 Type: Article Affiliation country: Brazil Institution/Affiliation country: Hospital de Clínicas de Porto Alegre/BR / Universidade Federal de Ciências da Saúde de Porto Alegre/BR / Universidade Federal do Rio Grande do Sul/BR