The influence of hydroxyurea on oxidative stress in sickle cell anemia

Abstract

Objective The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. MethodsOxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. ResultsThiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). ConclusionSickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals.

Serum Paraoxonase Activity and Malondialdehyde Serum Concentrations Remain Unaffected in Response to Hydroxyurea Therapy inβ-Thalassemia Patients

“…10 HU is suggested to produce direct oxidant and indirect antioxidant effects 30 ; however, there have been contradictory reports regarding the protective role of HU therapy in SCD patients. [23][24][25][26] To examine the possible proactive role of HU treatment on oxidative imbalance in β-thalassemia, we studied oxidative stress biomarkers.…”

“…Although the underlying mechanisms for the development of oxidative stress in SCD and β-thalassemia are different, 31 the oxidant/antioxidant ratio seems to be more affected in the latter. 14 On the basis of thiobarbituric acid reactive substances (TBARS) and GSH analysis, a few studies reported an antioxidant role of HU in SCD subjects; 23,24 however, investigations on MDA, 25,26 PON1, 26 and vitamin E 26 have suggested that oxidative damage among SCD patients was independent of HU therapy. It was also argued that the observed discrepancy regarding antioxidant effects of HU therapy might be due to the short treatment period.…”

“…22 HU therapy has been shown to induce GSH concentrations and to reduce lipid peroxidation in SCD patients, thus acting as a protective agent against oxidative stress. 23,24 However, there have been contradicting reports regarding the protective role of HU therapy on oxidative imbalance among SCD patients. 25,26 This potential effect of HU on oxidative stress in β-thalassemia subjects has not been investigated to date.…”

Influence of βS allele in the lipid peroxidation and antioxidant capacity parameters

“…This effect can probably be at increased Hb F and other actions of HU . The Hb F concentration increase inhibits the polymerization and sickling of Hb S, which attenuates the oxidants production, thus playing the protecting effect against LPO and hemolysis .…”

Comment on "The influence of hydroxyurea on oxidative stress in sickle cell anemia"

“…In this edition of the Revista Brasileira de Hematologia e Hemoterapia, Torres et al evaluate plasma markers of oxidative stress between SCD patients on and off HU, a topic that has been only lightly investigated previously (14) . In a previous study, the same group showed that comparing SCD patients on chronic transfusion and chelation therapy to SCD patients on HU and chelation therapy, the latter had lower levels of markers of lipid peroxidation (15) .…”