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

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.