title: Serum Paraoxonase Activity and Malondialdehyde Serum Concentrations Remain Unaffected in Response to Hydroxyurea Therapy in β-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.
authors.affiliation: National Center for Proteomics, University of Karachi, Karachi, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zohaib
authors.affiliation: National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan.
authors.forename: Saqib H
authors.initials: SH
authors.lastname: Ansari
authors.affiliation: National Center for Proteomics, University of Karachi, Karachi, Pakistan.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Hashim
authors.affiliation: National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan.
authors.forename: Tahir S
authors.initials: TS
authors.lastname: Shamsi
authors.affiliation: National Center for Proteomics, University of Karachi, Karachi, Pakistan.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Zarina
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D006918:Hydroxyurea
keywords: arylesterase; hydroxyurea; malondialdehyde; oxidative stress; paraoxonase; β-thalassemia