Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload

Publication date: Available online 29 May 2017
Source:Clinical Biochemistry
Author(s): David Ivars, Maria Teresa Orero, Karla Javier, Laura Díaz-Vico, José Luis García-Giménez, Salvador Mena, Carmen Tormos, Mercedes Egea, Pedro Luis Pérez, Beatriz Arrizabalaga, María Ángeles Ruiz, Nuria Yagüe, Mar Tormo, Reyes Sancho-Tello, Angela Gomes, Carmen Algueró, José Enrique O'Connor, Guillermo T. Sáez, Félix Carbonell, Rosa Collado
ObjectiveTo 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).MethodsWe examined the levels of superoxide anion (O2⁻), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), 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.ResultsPatients with IOL showed higher O2⁻ 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 2.7nmol/ml/min, p=0.0023; GPx: 50.9 vs 76.4nmol/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 (ΔΨm: 3.6 vs 6.4 MFI, p=0.0225). Finally, increased levels of 8-oxo-dG were detected in both groups of patients.ConclusionOxidative stress is an important but non-static phenomenon in MDS disease, whose status is influenced by, among other factors, the presence of injurious iron.



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