Experimental evidence of oxidative stress in patients with L-2-hydroxyglutaric aciduria and that L-carnitine attenuates in vitro DNA damage caused by D-2-hydroxyglutaric and L-2-hydroxyglutaric acids
| Autor: | Tatiane Cristina Hauschild, Eduard A. Struys, Carmen Regla Vargas, Vanusa Manfredini, Carlos Eduardo Diaz Jacques, Ângela Sitta, Moacir Wajner, Daiane Rodrigues, Abdellatif Bakkali, Cornelis Jakobs, Daniella de Moura Coelho |
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| Přispěvatelé: | Laboratory Medicine, AGEM - Inborn errors of metabolism, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Neuroscience - Cellular & Molecular Mechanisms |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Guanine Adolescent DNA damage Oxidative phosphorylation Toxicology medicine.disease_cause Dinoprost Protective Agents Glutarates 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Carnitine medicine Leukocytes Humans Child Reactive nitrogen species chemistry.chemical_classification Brain Diseases Metabolic Inborn General Medicine Reactive Nitrogen Species Oxidative Stress 030104 developmental biology Enzyme chemistry Biochemistry Child Preschool Tyrosine Comet Assay 030217 neurology & neurosurgery Oxidative stress DNA medicine.drug DNA Damage |
| Zdroj: | Rodrigues, D G B, de Moura Coelho, D, Sitta, Â, Jacques, C E D, Hauschild, T, Manfredini, V, Bakkali, A, Struys, E A, Jakobs, C, Wajner, M & Vargas, C R 2017, ' Experimental evidence of oxidative stress in patients with L-2-hydroxyglutaric aciduria and that L-carnitine attenuates in vitro DNA damage caused by D-2-hydroxyglutaric and L-2-hydroxyglutaric acids ', Toxicology in Vitro, vol. 42, pp. 47-53 . https://doi.org/10.1016/j.tiv.2017.04.006 Toxicology in Vitro, 42, 47-53. Elsevier Limited |
| ISSN: | 0887-2333 |
| DOI: | 10.1016/j.tiv.2017.04.006 |
| Popis: | D-2-hydroxyglutaric (D-2-HGA) and L-2-hydroxyglutaric (L-2-HGA) acidurias are rare neurometabolic disorders biochemically characterized by increased levels of D-2-hydroxyglutaric acid (D-2-HG) and L-2-hydroxyglutaric acid (L-2-HG) respectively, in biological fluids and tissues. These diseases are caused by mutations in the specific enzymes involved in the metabolic pathways of these organic acids. In the present work, we first investigated whether D-2-HG and L-2-HGA could provoke DNA oxidative damage in blood leukocytes and whether L-carnitine (LC) could prevent the in vitro DNA damage induced by these organic acids. It was verified that 50 μM of D-2-HG and 30 μM of L-2-HG significantly induced DNA damage that was prevented by 30 and 150 μM of LC. We also evaluated oxidative stress parameters in urine of L-2-HGA patients and observed a significant increase of oxidized guanine species and di-tyrosine, biomarkers of oxidative DNA and protein damage, respectively. In contrast, no significant changes of urinary isoprostanes and reactive nitrogen species levels were observed in these patients. Taken together, our data indicate the involvement of oxidative damage, especially on DNA, in patients affected by these diseases and the protective effect of LC. |
| Databáze: | OpenAIRE |
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