Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload
Por:
Ivars D, Orero MT, Javier K, Díaz-Vico L, García-Giménez JL, Mena S, Tormos C, Egea M, Pérez PL, Arrizabalaga B, Ruiz MÁ, Yagüe N, Tormo M, Sancho-Tello R, Gomes A, Algueró C, O'Connor JE, Sáez GT, Carbonell F and Collado R
Publicada:
1 nov 2017
Ahead of Print:
29 may 2017
Resumen:
Objective: To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL).
Methods: We examined the levels of superoxide anion (O-2 center dot(-)), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (Delta Psi m), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects.
Results: Patients with IOL showed higher O-2 center dot(-) levels (39.4 MFI) than normal controls (22.7 MFI, p = 0.0356) and patients at diagnosis (19.4 MFI, p = 0.0049). Antioxidant systems, except SOD activity, exhibited significant changes in IOL patients with respect to controls (CAT: 7.1 vs 2.7 nmol/ml/min, p = 0.0023; GPx: 50.9 vs 76.4 nmol/ml/min, p = 0.0291; GSH: 50.2 vs 24.1 MFI, p = 0.0060). Furthermore, mitochondrial dysfunction was only detected in IOL cases compared to controls (Delta Psi m: 3.6 vs 6.4 MFI, p = 0.0225). Finally, increased levels of 8-oxo-dG were detected in both groups of patients.
Conclusion: Oxidative stress is an important but non-static phenomenon in MDS disease, whose status is influenced by, among other factors, the presence of injurious iron.
Filiaciones:
:
Department of Medicine, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain.
Orero MT:
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain
Javier K:
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain
Díaz-Vico L:
Department of Biochemistry, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
García-Giménez JL:
CIBERER, The Biomedical Network Research Centre on Rare Diseases, Calle Álvaro de Bazán 10, 46010, Valencia, Spain
Mena S:
Department of Physiology, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
Tormos C:
Department of Biochemistry, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
Egea M:
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain
Pérez PL:
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain
Arrizabalaga B:
Service of Haematology, Hospital Universitario de Cruces, Plaza de Cruces 12, 48903 Barakaldo, Vizcaya, Spain
:
Service of Haematology, Hospital Francesc de Borja, Av. Medicina 6, 46702 Gandía, Valencia, Spain
:
Service of Haematology, Hospital Francesc de Borja, Av. Medicina 6, 46702 Gandía, Valencia, Spain
Tormo M:
Service of Haematology, Hospital Clínico Universitario, Av. Blasco Ibáñez 17, 46010, Valencia, Spain
:
Service of Haematology, Hospital Arnau de Vilanova, Calle Sant Clement 12, 46015, Valencia, Spain
Gomes A:
Department of Biochemistry, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
Algueró C:
Department of Biochemistry, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
O'Connor JE:
Department of Biochemistry, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
:
Service of Clinical Analyses, Hospital Universitario Doctor Peset, Av. Gaspar Aguilar 90, 46017, Valencia, Spain
Carbonell F:
Department of Medicine, Universitat de València, Av. Blasco Ibáñez 15, 46010, Valencia, Spain
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain
Collado R:
Service of Haematology, Hospital General Universitario de Valencia, Av. Tres Cruces 2, 46014, Valencia, Spain
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