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
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 seco...
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| Format: | Article |
| Language: | English |
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Hospital de Clinicas de Porto Alegre ; Universidade Federal do Rio Grande do Sul (UFRGS)
2018-04-01
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| Series: | Clinical and Biomedical Research |
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| Online Access: | http://seer.ufrgs.br/index.php/hcpa/article/view/76977 |
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| author | Camila Simioni Vanzin Caroline Paula Mescka Bruna Donida Desirèe Padilha Marchetti Carlos Eduardo Jacques Tatiane Hauschild Jéssica Lamberty Faverzani Marion Deon Dinara Moura Jenifer Saffi Daniella de Moura Coelho Moacir Wajner Angela T.S. Wyse Carmen Regla Vargas |
| author_facet | Camila Simioni Vanzin Caroline Paula Mescka Bruna Donida Desirèe Padilha Marchetti Carlos Eduardo Jacques Tatiane Hauschild Jéssica Lamberty Faverzani Marion Deon Dinara Moura Jenifer Saffi Daniella de Moura Coelho Moacir Wajner Angela T.S. Wyse Carmen Regla Vargas |
| author_sort | Camila Simioni Vanzin |
| collection | DOAJ |
| 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.
Keywords: Cystathionine-β-synthase deficiency; oxidative stress; 8-oxo-7,8-dihydro- 2’-deoxyguanosine; homocysteine; DNA damage; N-acetyl-L-cysteine |
| first_indexed | 2024-12-13T12:30:37Z |
| format | Article |
| id | doaj.art-b36ae36dd098482790e2470350a1ab3d |
| institution | Directory Open Access Journal |
| issn | 0101-5575 2357-9730 |
| language | English |
| last_indexed | 2024-12-13T12:30:37Z |
| publishDate | 2018-04-01 |
| publisher | Hospital de Clinicas de Porto Alegre ; Universidade Federal do Rio Grande do Sul (UFRGS) |
| record_format | Article |
| series | Clinical and Biomedical Research |
| spelling | doaj.art-b36ae36dd098482790e2470350a1ab3d2022-12-21T23:46:02ZengHospital de Clinicas de Porto Alegre ; Universidade Federal do Rio Grande do Sul (UFRGS)Clinical and Biomedical Research0101-55752357-97302018-04-0138136854DNA 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‑cysteineCamila Simioni Vanzin0Caroline Paula Mescka1Bruna Donida2Desirèe Padilha Marchetti3Carlos Eduardo Jacques4Tatiane Hauschild5Jéssica Lamberty Faverzani6Marion Deon7Dinara Moura8Jenifer Saffi9Daniella de Moura Coelho10Moacir Wajner11Angela T.S. Wyse12Carmen Regla Vargas13Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil. Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA). Porto Alegre, RS, Brasil.Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA). Porto Alegre, RS, Brasil.Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.Postgraduate Program in Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA). Porto Alegre, RS, Brasil.Postgraduate Program in Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.Laboratory of Toxicological Genetics, Universidade Federal de Ciências de Saúde de Porto Alegre (UFCSPA). Porto Alegre, RS, Brasil.Laboratory of Toxicological Genetics, Universidade Federal de Ciências de Saúde de Porto Alegre (UFCSPA). Porto Alegre, RS, Brasil.Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA). Porto Alegre, RS, Brasil.Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil. Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA). Porto Alegre, RS, Brasil.Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.Postgraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil. Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA). Porto Alegre, RS, Brasil. Postgraduate Program in Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre, RS, Brasil.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. Keywords: Cystathionine-β-synthase deficiency; oxidative stress; 8-oxo-7,8-dihydro- 2’-deoxyguanosine; homocysteine; DNA damage; N-acetyl-L-cysteinehttp://seer.ufrgs.br/index.php/hcpa/article/view/76977Cystathionine-β-synthase deficiencyoxidative stress8-oxo-7,8-dihydro- 2’-deoxyguanosinehomocysteineDNA damageN-acetyl-L-cysteine |
| spellingShingle | Camila Simioni Vanzin Caroline Paula Mescka Bruna Donida Desirèe Padilha Marchetti Carlos Eduardo Jacques Tatiane Hauschild Jéssica Lamberty Faverzani Marion Deon Dinara Moura Jenifer Saffi Daniella de Moura Coelho Moacir Wajner Angela T.S. Wyse Carmen Regla Vargas 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 Clinical and Biomedical Research Cystathionine-β-synthase deficiency oxidative stress 8-oxo-7,8-dihydro- 2’-deoxyguanosine homocysteine DNA damage 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 |
| 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_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_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 |
| topic | Cystathionine-β-synthase deficiency oxidative stress 8-oxo-7,8-dihydro- 2’-deoxyguanosine homocysteine DNA damage N-acetyl-L-cysteine |
| url | http://seer.ufrgs.br/index.php/hcpa/article/view/76977 |
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