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Original Article

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Blood Res 2023; 58(4):

Published online December 31, 2023

https://doi.org/10.5045/br.2023.2023174

© The Korean Society of Hematology

The association of pro-oxidant/antioxidant balance and blood parameters in patients with beta-thalassemia major: a cross-sectional study

Maryam Parvizi1, Maryam Deldadeh Moghaddam1, Shiva Nazari2, Hami Ashraf3, Maryam Kazemi Aghdam1

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1Pediatric Pathology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Science, 2Department of Pediatric Hematology and Oncology, Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Science, 3Digestive Research Institute, Tehran University of Medical Science, Tehran, Iran

Correspondence to : Maryam Deldadeh Moghaddam, M.D.
Pediatric Pathology Research Center, Shahid Beheshti University of Medical Science, Arabi Ave, Daneshjoo Blvd, Velenjak, Tehran 4631-19395, Iran
E-mail: moghaddam_mahsa@yahoo.com

*This study was supported by the Pediatric Pathology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Science, Tehran, Iran.

Received: September 19, 2023; Revised: November 19, 2023; Accepted: December 5, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background
Oxidative stress due to iron accumulation in patients with beta-thalassemia major (BTM) causes complications such as tissue damage and destruction. This study aimed to assess the association between the serum prooxidant/antioxidant balance (PAB) and blood parameters in patients with BTM.
Methods
This cross-sectional study included 92 patients with BTM. In this study, PAB was measured using an enzyme-linked immunosorbent assay (ELISA). Serum ferritin, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), thyroid-stimulating hormone (TSH), total cholesterol (TC), triglyceride (TG), complete blood cell count (CBC), and history of blood transfusion were recorded. The association of the blood parameters was assessed across the tertiles (T) of serum PAB (highest T vs. lowest T).
Results
The results showed that high serum ferritin was directly associated with serum PAB [odds ratio (OR), 12.80; 95% confidence interval (CI), 2.98‒54.91; T3 vs. T1]. Also, direct associations were found for high TC (OR, 4.97; 95% CI, 1.42‒17.32; T3 vs. T1), high ALT (OR, 4.95; 95% CI, 1.33‒18.46; T3 vs. T1) and high TSH (OR, 3.78; 95% CI, 1.10‒13.02; T3 vs. T1).
Conclusion
The findings of the present study showed that serum PAB levels were directly associated with ferritin, ALT, TC, and TSH levels. This indicates that improvements in blood parameters, especially ferritin and TSH levels, occur by ameliorating oxidative stress in patients with BTM.

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Keywords: Beta-thalassemia, Antioxidants, Oxidants, Oxidative stress

Article

Original Article

Blood Res 2023; 58(4): 201-207

Published online December 31, 2023 https://doi.org/10.5045/br.2023.2023174

Copyright © The Korean Society of Hematology.

The association of pro-oxidant/antioxidant balance and blood parameters in patients with beta-thalassemia major: a cross-sectional study

Maryam Parvizi1, Maryam Deldadeh Moghaddam1, Shiva Nazari2, Hami Ashraf3, Maryam Kazemi Aghdam1

1Pediatric Pathology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Science, 2Department of Pediatric Hematology and Oncology, Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Science, 3Digestive Research Institute, Tehran University of Medical Science, Tehran, Iran

Correspondence to:Maryam Deldadeh Moghaddam, M.D.
Pediatric Pathology Research Center, Shahid Beheshti University of Medical Science, Arabi Ave, Daneshjoo Blvd, Velenjak, Tehran 4631-19395, Iran
E-mail: moghaddam_mahsa@yahoo.com

*This study was supported by the Pediatric Pathology Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Science, Tehran, Iran.

Received: September 19, 2023; Revised: November 19, 2023; Accepted: December 5, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
Oxidative stress due to iron accumulation in patients with beta-thalassemia major (BTM) causes complications such as tissue damage and destruction. This study aimed to assess the association between the serum prooxidant/antioxidant balance (PAB) and blood parameters in patients with BTM.
Methods
This cross-sectional study included 92 patients with BTM. In this study, PAB was measured using an enzyme-linked immunosorbent assay (ELISA). Serum ferritin, blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), thyroid-stimulating hormone (TSH), total cholesterol (TC), triglyceride (TG), complete blood cell count (CBC), and history of blood transfusion were recorded. The association of the blood parameters was assessed across the tertiles (T) of serum PAB (highest T vs. lowest T).
Results
The results showed that high serum ferritin was directly associated with serum PAB [odds ratio (OR), 12.80; 95% confidence interval (CI), 2.98‒54.91; T3 vs. T1]. Also, direct associations were found for high TC (OR, 4.97; 95% CI, 1.42‒17.32; T3 vs. T1), high ALT (OR, 4.95; 95% CI, 1.33‒18.46; T3 vs. T1) and high TSH (OR, 3.78; 95% CI, 1.10‒13.02; T3 vs. T1).
Conclusion
The findings of the present study showed that serum PAB levels were directly associated with ferritin, ALT, TC, and TSH levels. This indicates that improvements in blood parameters, especially ferritin and TSH levels, occur by ameliorating oxidative stress in patients with BTM.

Keywords: Beta-thalassemia, Antioxidants, Oxidants, Oxidative stress

Fig 1.

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Figure 1.An illustration for measurement of the serum PAB (A) and its basis (B).Abbreviations: HCL, hydrochloride; OD, optical density; PAB, pro-oxidant antioxidant balance; TMB, tetrame-thylbenzidine.
Abbreviations: HCL, hydrochloride; OD, optical density; PAB, pro-oxidant antioxidant balance; TMB, tetramethylbenzidine.
Blood Research 2023; 58: 201-207https://doi.org/10.5045/br.2023.2023174

General characteristics and serum parameters of the study population (N=92)..


VariablesValues
Age (year)19.00±9.08
Transfusion number (per year)14.29±2.24
Female [frequency (%)]47 (51.1%)
WBC (NO. per L)7.97±5.51
RBC (NO. per µL)3.45±0.35
Hb (gr/dL)9.57±0.86
Hct (%)28.08±2.65
MCV (femtoliter)81.35±3.73
MCH (pg/cell)27.74±1.36
MCHC (gr/dL)29.56±1.43
Platelet (NO. per µL)310.28±124.88
BUN (mg/dL)16.49±5.03
Cr (mg/dL)0.85±0.23
TC (mg/dL)104.52±25.10
TG (mg/dL)125.26±60.19
Ferritin (µg/L)1,683±1,481
AST (U/L)28.06±13.93
ALT (U/L)22.47±15.27
TSH (mIU/L)3.09±1.70
PAB (HK units)38.38±24.92

Data are presented as mean±SD and frequency (percent) for quantitative and qualitative variables, respectively..

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BTM, beta-thalassemia major; BUN, blood urea nitrogen; Hb, hemoglobin; Hct, Hematocrit; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; PAB, pro-oxidant/ antioxidant balance; RBC, red blood cell; TC, total cholesterol; TG, triglyceride; TSH, thyroid-stimulating hormone; WBC, white blood cell..

The comparison of blood parameters of BTM patients across the tertiles of serum PAB..


VariablesTertiles of serum PABP
T1 (N=30; range, 0.00–25.00 HK units)T2 (N=31; range, 25.00–48.00 HK units)T3 (N=31; range, 48.00–100.00 HK units)
Age (year)21.80±6.8217.33±10.0217.90±9.670.116a)
Transfusion number (per year)14.57±1.3314.61±2.6913.71±2.410.207a)
Female [frequency (%)]6 (20.00)21 (67.70)20 (64.50)<0.001b)
WBC (NO. per L)8.35±7.626.45±1.549.12±5.450.148a)
RBC (NO. per µL)3.51±0.323.40±0.353.46±0.370.459a)
Hb (gr/dL)9.67±0.699.48±0.909.58±0.980.691a)
Hct (%)28.36±2.3027.88±2.7228.02±2.940.768a)
MCV (femtoliter)80.87±4.0482.09±3.4481.08±3.700.395a)
MCH (pg/cell)27.58±1.3527.89±1.1927.75±1.540.682a)
MCHC (gr/dL)29.62±1.4829.45±0.9329.63±1.780.855a)
Platelet (NO. per µL)305.90±128.91294.35±108.77310.28±124.880.514a)
BUN (mg/dL)16.18±4.3017.27±4.9916.01±5.740.447a)
Cr (mg/dL)0.93±0.270.77±0.180.84±0.200.019a)
TC (mg/dL)88.00±22.40107.13±20.92117.90±22.90<0.001a)
TG (mg/dL)145.97±67.02115.00±57.56115.48±51.970.070a)
Ferritin (µg/L)973±5851,773±1,3102,281±1,9290.002a)
AST (U/L)28.48±13.2123.58±10.5632.13±16.430.051a)
ALT (U/L)18.33±8.3820.74±15.2828.19±18.770.029a)
TSH (mIU/L)2.94±1.732.81±1.713.51±1.640.222a)

Data are presented as mean±SD for quantitative variables and frequency (percent) for qualitative variables..

a)Data analysis was done by ANOVA test. b)Data analysis was done by chi-square test..

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BTM, beta-thalassemia major; BUN, blood urea nitrogen; Hb, hemoglobin; Hct, hematocrit; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; PAB, pro-oxidant/antioxidant balance; RBC, red blood cell; TC, total cholesterol; TG, triglyceride; TSH, thyroid-stimulating hormone; WBC, white blood cell..

The association of blood parameters and serum PAB..


VariablesTertiles of serum PABPfor trends
T1
(N=30; range, 0.00–25.00 HK units)		T2
(N=31; range, 25.00–48.00 HK units)		T3
(n=31; range, 48.00–100.00 HK units)
High ferritin (>1,200 µg/L)Median8881,2941,8000.001
High/total (%)9/31 (30)17/31 (54.8)19/31 (61.3)
Crude modelRef.3.80 (1.29; 11.19)5.00 (1.67; 14.92)
Adjusted modela)Ref.9.45 (2.22; 40.10)12.80 (2.98; 54.91)
High BUN (>16 mg/dL)Median16.3515.8715.400.915
High/total (%)16/30 (53.3)15/31 (48.4)15/31 (48.4)
Crude modelRef.0.820 (0.300; 2.24)0.820 (0.300; 2.24)
Adjusted modela)Ref.0.87 (0.26; 2.84)0.93 (0.29; 2.95)
High Cr (>0.8 mg/dL)Median0.930.750.800.514
High/total (%)20/30 (66.7)12/31 (38.7)13/31 (41.9)
Crude modelRef.0.31 (0.11; 0.91)0.36 (0.12; 1.02)
Adjusted modela)Ref.0.60 (0.17; 2.06)0.65 (0.19; 2.23)
High TC (>104 mg/dL)Median85.00111.00116.000.012
High/total (%)8/30 (26.7)17/31 (54.8)21/31 (67.7)
Crude modelRef.3.33 (1.14; 9.78)5.77 (1.91; 17.44)
Adjusted modela)Ref.2.81 (0.80; 9.84)4.97 (1.42; 17.32)
High TG (>108 mg/dL)Median129.50106.0099.000.999
High/total (%)18/30 (60)14/31 (45.2)14/31 (45.2)
Crude modelRef.0.54 (0.19; 1.51)0.54 (0.19; 1.51)
Adjusted modela)Ref.1.27 (0.37; 4.33)1.01 (0.30; 3.35)
High AST (>25 U/L)Median25.0022.0028.000.281
High/total (%)16/30 (53.3)11/31 (35.5)20/31 (64.50)
Crude modelRef.0.48 (0.17; 1.34)1.59 (0.56; 4.44)
Adjusted modela)Ref.0.38 (0.09; 1.47)1.93 (0.53; 7.02)
High ALT (>18 U/L)Median17.0017.0022.000.014
High/total (%)14/30 (46.7)12/31 (38.7)21/31 (67.7)
Crude modelRef.0.72 (0.26; 1.99)2.40 (0.84; 6.79)
Adjusted modela)Ref.1.39 (0.39; 4.89)4.95 (1.33; 18.46)
High TSH (>2.8 mIU/L)Median2.462.563.420.033
High/total (%)10/30 (33.33)15/31 (48.4)21/31 (67.7)
Crude modelRef.1.87 (0.66; 5.28)4.20 (1.44; 12.23)
Adjusted modela)Ref.1.74 (0.508; 5.98)3.78 (1.10; 13.02)
High Platelet (>284 NO. per µL)Median2802713220.216
High/total (%)13/30 (43.3)14/31 (45.2)19/31 (61.3)
Crude modelRef.1.07 (0.39; 2.95)2.07 (0.74; 5.75)
Adjusted modela)Ref.1.12 (0.32; 3.91)2.16 (0.62; 7.45)
High WBC (>6.6 NO. per L)Median6.006.507.800.328
High/total (%)13/30 (43.3)13/31 (41.9)20/31 (64.5)
Crude modelRef.0.94 (0.34; 2.60)2.37 (0.84; 6.66)
Adjusted modela)Ref.0.78 (0.23; 2.60)1.72 (0.53; 5.56)
High RBC (>3.38 NO. per µL)Median3.383.383.460.638
High/total (%)14/30 (46.7)15/30 (48.4)16/30 (51.6)
Crude modelRef.1.07 (0.39; 2.92)1.21 (0.44; 3.33)
Adjusted modela)Ref.0.69 (0.21; 2.32)0.74 (0.22; 2.42)
High Hb (>9.5 gr/dL)Median9.599.609.700.939
High/total (%)15/30 (50)16/31 (51.6)16/31 (51.6)
Crude modelRef.1.06 (0.39; 2.91)1.06 (0.39; 2.91)
Adjusted modela)Ref.1.06 (0.32; 3.45)0.96 (0.30; 3.05)
High Hct (>28.1%)Median28.1528.0028.300.920
High/total (%)15/30 (50)15/31 (48.4)17/31 (54.8)
Crude modelRef.0.93 (0.34; 2.55)1.21 (0.44; 3.32)
Adjusted modela)Ref.0.74 (0.22; 4.41)0.92 (0.29; 2.93)
High MCV (>81.82 femtoliter)Median81.6881.9481.720.706
High/total (%)15/30 (50)16/31 (51.6)15/31 (48.4)
Crude modelRef.1.06 (0.39; 2.91)0.93 (0.34; 2.55)
Adjusted modela)Ref.0.88 (0.27; 2.82)0.80 (0.25; 2.51)
High MCH (>28 pg/cell)Median27.8128.2428.000.629
High/total (%)13/30 (43.3)18/31 (58.1)15/31 (48.4)
Crude modelRef.1.81 (0.65; 4.99)1.22 (0.44; 3.36)
Adjusted modela)Ref.1.13 (0.33; 3.80)0.76 (0.23; 2.50)
High MCHC (>29.28 gr/dL)Median29.4729.4729.150.742
High/total (%)16/30 (53.3)16/31 (51.6)15/31 (48.4)
Crude modelRef.0.93 (0.34; 2.55)0.82 (0.30; 2.24)
Adjusted modela)Ref.0.91 (0.28; 2.92)0.82 (0.26; 2.59)

Data analysis was done by logistic binary regression..

a)Age, sex and transfusion number were adjusted as potential covariates..

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BTM, beta-thalassemia major; BUN, blood urea nitrogen; Hb, hemoglobin; Hct, hematocrit; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; PAB, pro-oxidant/antioxidant balance; RBC, red blood cell; TC, total cholesterol; TG, triglyceride; TSH, thyroid-stimulating hormone; WBC, white blood cell..
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