Homocysteine contribution to DNA damage in cystathionine β-synthase-deficient patients |
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Authors: | Camila Simioni Vanzin Vanusa Manfredini Ana Eveline Marinho Giovana Brondani Biancini Graziela Schmitt Ribas Marion Deon Angela Terezinha de Souza Wyse Moacir Wajner Carmen Regla Vargas |
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Institution: | 1. Programa de Pós-Graduação em Ciências Biológicas, Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS 90035-000, Brazil;2. Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil;3. Programa de Pós-Graduação em Bioquímica da Universidade Federal do Pampa (UNIPAMPA), BR 472, Km 585, Uruguaiana, RS 97500-970, Brazil |
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Abstract: | High blood levels of homocysteine (Hcy) are found in patients affected by homocystinuria, a genetic disorder caused by deficiency of cystathionine β-synthase (CBS) activity, as well as in nutritional deficiencies (vitamin B12 or folate) and in abnormal renal function. We previously demonstrated that lipid and protein oxidative damage is increased and the antioxidant defenses diminished in plasma of CBS-deficient patients, indicating that oxidative stress is involved in the pathophysiology of this disease. In the present work, we extended these investigations by evaluating DNA damage through the comet assay in peripheral leukocytes from CBS-deficient patients, as well as by analyzing of the in vitro effect of Hcy on DNA damage in white blood cells. We verified that DNA damage was significantly higher in the CBS-deficient patients under treatment based on a protein-restricted diet and pyridoxine, folic acid, betaine and vitamin B12 supplementation, when compared to controls. Furthermore, the in vitro study showed a concentration-dependent effect of Hcy inducing DNA damage. Taken together, the present data indicate that DNA damage occurs in treated CBS-deficient patients, possibly due to high Hcy levels. |
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Keywords: | CAT catalase CBS cystathionine β-synthase DI damage index Hcy homocysteine LC&ndash MS/MS liquid chromatography electrospray tandem mass spectrometry MTHFR methylenetetrahydrofolate reductase ROS reactive oxygen species SAH S-adenosylhomocysteine SOD superoxide dismutase SPSS Statistical Package for the Social Sciences tHcy total homocysteine |
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