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

Abstract

β-Thalassemia is the most common hereditary disorder characterized by reduced production of β-globin chains of hemoglobin A (HbA). In recent years, hydroxyurea (HU) has shown promising therapeutic benefits in patients with β-thalassemia by fetal hemoglobin augmentation. We have analyzed effects of hydroxyurea treatment on oxidative stress in β-thalassemia patients by assessing activities of paraoxonase (PON) and arylesterase along with malondialdehyde (MDA) and total reactive oxygen species (ROS) concentrations. Blood samples from 159 individuals including 56 HU-treated and 58 untreated β-thalassemia patients and 45 healthy controls were analyzed. PON activity was found to be highest in healthy individuals (177.76 ± 4.44 U/mL) as compared to treated (52.67 ± 3.65 U/mL) and untreated (55.11 ± 3.26 U/mL) patients. A similar trend was observed in the case of arylesterase activity in normal, β-thalassemia-treated, and untreated (210.0 ± 11.25 U/mL, 163.03 ± 9.04 U/mL, 139.77 ± 10.10 U/mL) subjects. Serum MDA concentrations (2.59 ± 0.09 nmol/mL, 2.45 ± 0.08 nmol/mL, and 1.15 ± 0.05 nmol/mL) and total ROS concentrations (3.73 ± 0.20 nmol/mL, 3.54 ± 0.23 nmol/mL, and 2.45 ± 0.14 nmol/mL) were significantly elevated in both groups (untreated and treated) as compared to healthy individuals (P < .01). Oxidative stress was found to be markedly elevated in β-thalassemia patients as compared to healthy controls. Insignificant differences were, however, observed in mean concentrations of PON1 paraoxonase and arylesterase activities, serum MDA concentration and total ROS concentrations between HU-treated and untreated patients. We propose that HU therapy alone seems to be ineffective in managing oxidative stress and is likely to offer a better clinical outcome when supplemented with efficient iron chelation therapy and antioxidants.

Differentially expressed plasma proteins of β-thalassemia/hemoglobin E patients in response to curcuminoids/vitamin E antioxidant cocktails

“…Serum paraoxonase/arylesterase 1 (PON1) is an antioxidant enzyme carried on HDL that also hydrolyzes lipid peroxidation products in LDL [34]. Decreased activities of PON1 associated with increased oxidative stress, decreased Hb levels, and increased atherosclerosis risk have been reported in thalassemic patients [34][35][36][37]. Curcuminoids cocktail enhances PON1 intensities in correlation with decreased ROS levels, which was consistent with the ELISA results (Figure 2), supporting by a previous in vivo study [38].…”

“…Serum paraoxonase/arylesterase 1 (PON1) is an antioxidant enzyme carried on HDL that also hydrolyzes lipid peroxidation products in LDL [34]. Decreased activities of PON1 associated with increased oxidative stress, decreased Hb levels, and increased atherosclerosis risk have been reported in thalassemic patients [34][35][36][37].…”

Polyneuropathy Associated with Severe Iron Overload and Oxidative Stress in β-Thalassemia Patients

“…Our further analyses showed that peripheral neuropathy score (TNSn) correlated positively with transfusion frequency and serum ferritin; highlighting an association between severe iron overload and motor neuropathy which was further proved by the regression analysis model. B-thalassemia patients were recently proved to have a higher rate of ROS production with subsequent oxidative stress [17,18]. This may play a role in the pathogenesis of neurological dysfunction [19].…”

An Insight in Understanding the Symptomatology of β-Thalassaemia Major - II

“…on intracellular anti-oxidant levels, metabolic pathways, handling of trace elements required for enzymes in different metabolic pathways, oxygen binding and dissociation from haemoglobin-F are not entirely known. Our group has previously reported interesting results of proteomics, metallomics, metabolomics and genomics in β-thalassemia patients with and without the institution of HU [9][10][11][12][13]. Primary and secondary genetic modifiers, like beta globin gene mutations and presence or absence of XMN-1, HSB1L-MYB, and BCL-11A polymorphisms, have been found to significantly influence the response of HU in improving haemoglobin levels in beta thalassemia patients [14].…”

“…One important initial finding was that serum paraoxonase activity and malondialdehyde serum concentrations remain unaffected in response to hydroxyurea therapy in β-thalassemia patients [11]. This implies that HU does not adversely affect metabolic pathways in these patients.…”