Thalassemia major patients using iron chelators showed a reduced plasma thioredoxin level and reduced thioredoxin reductase activity, despite elevated oxidative stress

Abstract

In the present study, we aimed to investigate plasma levels of peroxiredoxin 2 (Prx2) and thioredoxin 1 (Trx1), and the activity of thioredoxin reductase (TrxR), in thalassemia major (TM) patients living in the Antalya region, Turkey. The patients were divided into three groups, according to chelators – the deferoxamine group (DFO, n = 20), the deferasirox group (DFX, n = 20), and the deferiprone group (DFP, n = 20), to compare any possible effect of chelators on antioxidative and oxidative stress parameters. A control group (n = 20) was selected from healthy volunteers. The activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and TrxR, as well as the concentrations of Prx2, Trx1, glucose-6-phosphate dehydrogenase (G-6-PD), reduced glutathione (GSH), hydrogen peroxide (H₂O₂), and malondialdehyde (MDA) were measured in the plasma samples of TM patients and the controls. The activity of CAT and the levels of H₂O₂ and MDA in the TM patients were significantly higher than those in the controls, while the levels of GPx, Trx1, TrxR, and GSH were lower. The concentrations of ferritin, GSH, H₂O_2, and MDA, as well as the activities of GR, CAT and TrxR, showed significant differences among the chelator groups. Although TrxR activity showed an increase in TM patients due to an elevated iron overload, both TrxR activity and Trx1 level were lower in the patient groups compared with the cases in the control group. As a result, because Trx1 level and TrxR activity were measured at a low level in the patients, increasing the levels of Trx1 and TrxR in TM patients will be a target of future treatment.

Keywords::

• Peroxiredoxin 2
• thioredoxin 1
• thalassemia major
• iron chelators
• oxidative stress

Acknowledgments

The authors would like to thank all members of the Pediatric Hematology Department, Akdeniz University Hospital, and the Hematology Department, Antalya Education and Research Hospital. The authors thank Deniz Özel for statistical calculations. The authors would like to give special thanks to the patients, parents, and healthy volunteers for their contribution to the study.

Author contributions

SG designed and coordinated the research study. ZO and GEG performed the experiments. AK and EK provided patients. SG, GEG and ZO participated in the data collection. SG and GEG performed the statistical analysis and drafted figures. SG and ZO wrote the paper. All authors read and approved the final manuscript.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by a grant (Project no: 112S657) from TÜBİTAK (The Scientific and Technological Research Council of Turkey).