The Indonesian Biomedical Journal, Vol.17, No.1, February 2025, p.1-108

RESEARCH ARTICLE

Print ISSN: 2085-3297, Online ISSN: 2355-9179

Lower Ferrum, Selenium, and Cadmium; Higher Chromium and Lead Levels in
Preeclampsia Patients’ Erythrocyte: A Cross-Sectional Study
Sandhy Prayudhana1, Damar Prasmusinto2,, Noroyono Wibowo2, Rima Irwinda2,
Yuditiya Purwosunu2, Yudianto Budi Saroyo2
1
Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jl. Salemba Raya No.6, Jakarta 10430, Indonesia
Maternal Fetal Division, Department of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital,
Jl. Salemba Raya No.6, Jakarta 10430, Indonesia

2

*Corresponding author. Email: damarprasmusinto@gmail.com
Received date: Aug 9, 2024; Revised date: Jan 24, 2025; Accepted date: Jan 31, 2025

Abstract

B

ACKGROUND: Oxidative stress and trace elements in erythrocytes are linked to impaired nitric oxide that can
lead to endothelial dysfunction in preeclampsia patients. The morphology of erythrocytes could also be affected by
oxidative stress and trace elements. While the relationships between erythrocyte index, superoxide dismutase (SOD)
activity, and oxidative stress in preeclampsia have been well established, less attention has been given to the erythrocyte trace
elements and their role in disease progression. This study was performed to examine the erythrocyte trace element profile in
women with preeclampsia, comparing it with controls. Additionally, it will explore the correlations between erythrocyte trace
element levels, the erythrocyte index, and SOD activity.
METHODS: A cross-sectional study was conducted involving 40 pregnant women consisting of those with severe
preeclampsia and normotensive. Erythrocytes was isolated from blood samples, and analysis of erythrocyte SOD activity and
trace elements were performed using the enzyme linked immunosorbent assay (ELISA) and inductively coupled plasma mass
spectrometry (ICP-MS), respectively.
RESULTS: Among 15 examined erythrocyte trace elements, the levels of ferrum (Fe), selenium (Se), and cadmium (Cd)
were significantly lower, meanwhile, the levels of chromium (Cr) and lead (Pb) were significantly higher in preeclampsia
subjects. Additionally, preeclampsia subjects exhibited smaller erythrocyte sizes compared to the normotensive subjects. The
erythrocyte SOD activity was significantly elevated in the preeclampsia subjects than the normotensive subjects.
CONCLUSION: Erythrocyte trace element levels of Fe, Se, Cd, Cr, and Pb were significantly altered in preeclampsia
compared to normotensive controls. These findings suggest that these trace elements may serve as potential predictors for
preeclampsia.
KEYWORDS: preeclampsia, trace elements, antioxidant, oxidative stress, superoxide dismutase, erythrocyte index
Indones Biomed J. 2025; 17(1): 70-7

Introduction

Preeclampsia is a major etiology of maternal and infant
morbidity and mortality worldwide. Based on the 2018
Basic Health Research in Indonesia, hypertension in
pregnancy is one of the three leading causes of maternal
70

morbidity and mortality, with a prevalence of around 2.7%.
(1) Until now, existing studies have not been able to fully
reveal the etiology and pathogenesis of preeclampsia.(2)
The pathophysiology of preeclampsia is closely related
to oxidative stress. It is generally recognized that oxidative
stress occurs in the placenta, trophoblast, or vascular
endothelium.(3,4) Abnormality was found in trophoblast

Copyright © 2025 The Prodia Education and Research Institute.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC-BY-NC) License.

DOI: 10.18585/inabj.v17i1.3257

Erythrocyte SOD Activity and Trace Elements in Preeclampsia (Prayudhana S, et al.)
Indones Biomed J. 2025; 17(1): 70-7

invasion to myometrium and endothelial dysfunction in
placenta, then spreads to maternal circulation.(5) However,
increased oxidative stress can also occur in plasma and
erythrocytes.(6) Maternal erythrocytes can play a role in
causing maternal endothelial dysfunction through impaired
nitric oxide (NO) balance.(7) Co-incubation of mice’s
aorta with erythrocytes of women with preeclampsia can
induce endothelial dysfunction. However, this event did not
occur in the erythrocytes of healthy pregnant women. This
suggests a role for erythrocytes in endothelial dysfunction
in preeclampsia patients.(7)
The main antioxidant systems in erythrocytes are
superoxide dismutase (SOD), glutathione, glutathione
peroxidase,
glutathione
S-transferase,
glutathione
reductase, and catalase.(8) These antioxidant enzymes need
trace elements such as selenium (Se), cuprum (Cu), zinc
(Zn), manganese (Mn), and ferrum (Fe) as co-factors for
the practical function of these enzymes. Oxidative stress
and trace elements in erythrocytes are essential in causing
impaired NO production.(8–11)
A recent literature study demonstrated the importance
of cellular wellness and nutrition in the incidence of
preeclampsia.(12) Maternal erythrocytes are important
in causing maternal endothelial dysfunction via oxidative
stress and trace elements. Until now, there is still no study
that evaluates the erythrocyte index, SOD activity, and
trace elements even though it is important to understand
the status of these parameters between preeclampsia and
normotensive pregnant women. Therefore, this study was
performed to examine the erythrocyte trace element profile
in women with preeclampsia and comparing it with controls.
The results of this study might help finding the best potential
predictors for preeclampsia.

Methods

Study Design and Subjects Recruitment
A cross-sectional study was conducted in Dr. Cipto
Mangunkusumo National Referral Hospital, Tangerang
Regional Hospital, and Koja Region Hospital from October
2020 to March 2021. The total subjects included in the
study was 40 pregnant women which were classified into
normotensive (n=20) and preeclampsia with severe features
(n=20). Patients with a gestational age of 20 weeks to term
that fulfill the criteria of preeclampsia with severe features
based on the American College of Obstetricians and
Gynecologists (ACOG) criteria were included in this study.
(13) Pregnant subjects with diabetes mellitus, heart disease,

hemoglobinopathy, autoimmune disease, or congenital
anomalies were excluded from the study. The protocol of
the study has been approved by the Ethical Committee
for Research in Human from the Faculty of Medicine,
Universitas Indonesia (No. KET—236/UN2.F1/ ETIK/
PPM.00.02/2021).
Sample Preparation and Erythrocyte Isolation
Blood samples were collected using venous puncture into
several tubes; 3 mL blood into EDTA tube, 6 mL blood into
sodium heparin containing tube, and 6 mL blood into plain
tube for various analysis. Initially, erythrocyte should be
isolated for the analysis of erythrocyte SOD activity and
trace elements. First, 2 mL of blood sample was pipetted into
a polypropylene tube with 2 mL of PBS and homogenized.
Then 3 mL of Ficoll-Paque Plus solution was added,
homogenized, and the sample was centrifuged at 400 g for
30 minutes at 19oC. After forming the erythrocyte layer and
supernatant, supernatant layer was removed, and 2 mL PBS
was added. The erythrocytes part was then washed 3 times
until cleaned by centrifugation at 100 g for 10 minutes. After
the last washing step, phosphate buffered saline (PBS) was
added to the final volume of 2 mL, and then the erythrocyte
sample was ready to use.
Erythrocyte Indices Measurement
Erythrocytes indices, including hemoglobin, hematocrit,
erythrocyte concentration, mean corpuscular volume
(MCV), mean corpuscular hemoglobin (MCH), mean
corpuscular hemoglobin concentration (MCHC), and red
cell distribution width–coefficient of variation (RDWCV) were extracted from a complete blood count that was
directly calculated using Sysmex SNL 550 (Syesmex,
Hyogo, Japan) with impedance and photometric methods.
Erythrocyte SOD Activity Measurement
Erythrocyte SOD was calculated using Superoxide
Dismutase Assay Kit (Catalogue No. 706002; Cayman
Chemical, Ann Arbor, MI, USA) and Microplate Reader
Biorad model 680 (Bio-rad Laboratories, Hercules, CA,
USA) with software Microplate Manager ver 5.2.1 (Bio-rad
Laboratories). Standard preparation for SOD calculation
using 20 µL of standard SOD and dissolved with 1.98
mL of sample buffer to obtain a stock solution of standard
SOD. Standard well SOD was made by adding 200 uL of
the dissolved Radical Detector and 10 µL of standard was
added per well to the plate. Whereas the sample was made
by adding 200 µL of the dissolved Radical Detector and
10 µL of the sample was added into the well. Dissolved
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The Indonesian Biomedical Journal, Vol.17, No.1, February 2025, p.1-108

xanthine oxidase was added immediately to all wells filled
with standards and samples. The plate was incubated for 30
minutes on a shaker at room temperature. The absorbance
was read at a wavelength of 450 nm using an enzyme linked
immunosorbent assay (ELISA) plate reader. The results
were calculated by calculating the average absorbance of
each standard and sample. The linear rate of the standard was
calculated based on the standard LR equation X = Standard
Abs X/Standard Abs A. The next step was calculation of the
linear rate of each sample based on the sample LR equation
X = Abs sample X/Standard Abs A. After both linear rates
were calculated, the linear rate of the standard was plot as a
function of final SOD activity (U/mL).
Trace Elements Calculation
The examined panel of erythrocyte trace elements consisted
of 15 variables, namely Vanadium (V), Cromium (Cr),
Molybdenum (Mo), Mn, Fe, Cobalt (Co), Nickel (Ni),
Cu, Zn, Se, Arsenic (As), Cadmium (Cd), Mercury (Hg),
Thalium (Tl), and Lead (Pb). The calculation of trace
elements was done using Agilent inductively coupled plasma
mass spectrometry (ICP-MS) 7700x (Agilent, Santa Clara,
CA, USA). Reference standard with ICP Multi-Element
Standard Solution VI (Cat. 5185-5959, Merck, Rahway,
NJ, USA), internal standards Indium Standard (Merck),
reagent Ammonium solution 25%, Tritiplex III, Trition
X, 1-Butanol, and Nitric acid 65% were used. One mL of
erythrocyte sample was lysed with the addition of 1 mL of
cold water, then the sample was diluted with a dilution factor
of 100 times with an alkaline solution containing an internal
standard of Indium for examination of metals V, Cr, Mn.
Fe, Co, Ni, Cu, Zn, Se. Then, it was diluted 20 times with
alkaline solution containing an internal standard of Indium
for examination of metals As, Cd, Hg, Tl, Pb. Lastly, it was
injected into the ICP-MS 7700x system with the MassHunter
software (Agilent). The measurement of trace elements
was carried out quantitatively and calculated against the
standard using standard internal calculations. Erythrocyte
trace elements were measured using concentration per
erythrocyte. The examination was developed and validated
by the Mass Spectrometry Laboratory of PT. Prodia
Widyahusada for the research purpose only.

Results

Demographic Characteristics
The characteristics of the subject, including maternal age,
maternal education, maternal occupation, blood pressure,
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Print ISSN: 2085-3297, Online ISSN: 2355-9179

gestational age, and body mass index (BMI) were presented
in Table 1. There were differences in the level of education
and blood preassure (both sistolic and diastolic) of
preeclampsia subjects compared to normotensive subjects
(p<0.05). For the BMI, most of preeclampsia subjects tend to
be overweight or obese (65%), meanwhile in normotensive
subjects most subjects had normal BMI (50%) followed by
overweight or obese (45%).
Erythrocyte Index
Significant differences were found in the erythrocyte, MCV,
MCH, and MCHC variables. The mean value of erythrocytes
in preeclampsia subjects was higher than the normotensive
subjects, with a mean difference of 0.55 million/mL (14.3%).
As for the values of MCV, MCH, and MCHC, preeclampsia
subjects had smaller values. This value indicated that the
preeclampsia subjects had a smaller erythrocyte size than
the normotensive subjects (Table 2).
Erythrocyte SOD Activity
Preeclampsia subjects had higher values of erythrocyte
SOD activity than the normotensive subjects, both in terms
of volume per mL of erythrocyte and per Hb. The difference
in mean erythrocyte SOD/mL was 6.84 U/mL (23.6%),
while SOD/Hb levels were 52.92 U/Hb (20.5%).
Erythrocyte Trace Elements Content
There were 15 variables of trace elements analyzed in this
study, and Table 3 showed an example of the results of
ICP-MS analysis results from one preeclampsia and one
normotensive subjects. Cr was not detected in all study
subjects. Five trace elements (V, Mo, Ni, Cd, and Tl)
in some study subjects were not detectable. V was only
detected in 6 preeclampsia subjects with a mean value of
0.27±0.55 g/g Hb. Meanwhile, in normotensive subjects,
V was only detected in 1 subject with 0.15 g/g Hb levels.
Mo was detected in 4 preeclampsia subjects with a median
value of 1.75 g/g Hb. Among the normotensive subjects,
Mo was only detected in 1 subjects with a value of 0.8 g/g
Hb. The levels of Ni, Cd, and Tl were not detected in the
preeclampsia and normotensive subject.
Based on the ICP-MS results, the levels of Fe, Co,
Se, Cd, and Pb were significantly different in preeclampsia
and normotensive subjects (Table 4). The levels of Fe, Se,
and Cd were lower in the preeclampsia subjects than in the
normotensive subjects, with differences of 10.6%, 14.7%,
and 69.7%, respectively. The levels of Co and Pb were
higher in the preeclampsia subjects, with a difference of
87.5% and 67.3%, respectively.

Erythrocyte SOD Activity and Trace Elements in Preeclampsia (Prayudhana S, et al.)
Indones Biomed J. 2025; 17(1): 70-7

DOI: 10.18585/inabj.v17i1.3257

Table 1. Characteristics of subjects.
Preeclampsia
(n=20)

Variable

Control
(n=20)

p -value
1.000

Parity, n (%)
Nuliparity

7 (35)

Multiparity

7 (35)

13 (65)

13 (65)

Age (year), median (min-max)

32.8 (23-40)

32.0 (21-40)

0.547b

Gestational age (weeks), median (min-max)

30.8 (23-37)

30.8 (23-39)

0.947b

Education, n (%)

0.008c,*

College/University

19 (95)

12 (60)

High school

1 (5)

8 (40)

Occupation, n (%)

0.292c

Housewive

19 (95)

17 (85)

Worker

1 (5)

3 (15)

Sistolic (mmHg), mean±SD

168.1±19.2

114.2±12.9

0.000a,*

Diastolic (mmHg), median (min-max)

108 (80-130)

74 (67-96)

0.000b,*

Body Mass Index, n (%)

c

0.324

Underweight (<18.5)

0 (0)

1 (5)

Normal (18.5-25.0)

7 (35)

10 (50)

13 (65)

9 (45)

Overweight/Obese (>25.0)

Tested with Independent T-test; Tested with Mann-Whitney U test; cTested with Chi Square test.
*Significant if p<0.05.
a

b

Correlation of Erythrocyte SOD Activity and Other
Variables
The correlation test of SOD activity on erythrocytes against
erythrocyte trace elements was shown in Table 5. Only SOD
levels with Fe levels had a significant negative correlation
(r=-0.370). The lower Fe levels in erythrocyte were
associated with increased SOD activity in erythrocyte. The
correlation test of SOD activity compared to the patient's

age or gestational age also gave a negative correlation with
r=-0.218 and r=-0.259, but it was not statistically significant.

Discussion

The results of this study showed that erythrocyte SOD
activity was higher in the preeclampsia subjects compared

Table 2. Distribution of complete peripheral blood in preeclampsia and control group.
Variable
Hemoglobin (mg/dL)
Hematocrite (%)

a

b

Erythrocyte (million/mL)
MCV (fL)

a

MCH (pg)

a

MCHC (%)
RDW-CV

a

b

Leukosit (/mL)

b

Platelet (thousand/mL)
ESR (mm/hour)

a

a

a

Preeclampsia

Control

p -value

11.7±1.44

11.3±0.94

0.292

35.8 (31.5-45.1)

33.7 (28.5-42.6)

0.072

4.39±0.55

3.84±0.44

0.001*

83.01±8.48

88.53±5.6

0.020*

26.9±3.6

29.6±5.7

0.009*

32.4±1.7

33.4±1.03

0.023*

14.3 (12.5-23.7)

14.1 (12-16.2)

0.448

13.65 (6.7-25.5)

11.8 (7.4-14.1)

0.056

281.8±122.9

258.4±56.8

0.446

52.35±27.1

52.65±22.2

0.97

Normally distributed data presented in mean±SD, the difference in the mean was calculated by
independent T-test. bNot normally distributed data presented in median (minimum-maximum
value), the median difference is calculated by the Mann-Whitney U test. *Significant if p<0.05.
a

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The Indonesian Biomedical Journal, Vol.17, No.1, February 2025, p.1-108

Print ISSN: 2085-3297, Online ISSN: 2355-9179

Table 3. An example of trace elements analysis using ICP-MS in normal and preeclampsia subject.
Normotensive Subject' Trace Elements
RT

Compound
Ni
Cd
Tl
V
Cr
Mn

Mass
60
111
205
51
52
55

Conc
1,043
0,023
0,145
0,369
<0.000
0,709

Units
ug/L
ug/L
ug/L
ug/L
ug/L
ug/L

Count
1.814
53
490
759
4.292
1.295

Quant by
Area
Area
Area
Area
Area
Area

Det
Pulse
Pulse
Pulse
Pulse
Pulse
Pulse

Ratio
3,72E-02
1,10E-03
1,01E-02
2,93E-02
1,66E-01
5,00E-02

ISTD
In
In
In
In
In
In

Fe
Co

56
59

44,775
0,126

ug/dL
ug/L

756.216
344

Area
Area

Analog
Pulse

2,96E+01
1,33E-02

In
In

Cu
Zn

63
66

1900,612
46,033

ug/L
ug/dL

2.962.639
166.750

Area
Area

Analog
Pulse

1,14E+02
6,49E+00

In
In

As
Se

75
78

2,3
97,078

ug/L
ug/L

1.011
4.832

Area
Area

Pulse
Pulse

3,91E-02
1,87E-01

In
In

Mo
Hg
Pb

95
202
208

0,622
1,62
0,008

ug/L
ug/L
ug/dL

1.657
860
866

Area
Area
Area

Pulse
Pulse
Pulse

3,35E-02

In

Preeclampsia Subject' Trace Elements
RT

Compound
Ni
Cd
Tl

Mass
60
111
205

Conc
1,252
0,008
0,152

Units
ug/L
ug/L
ug/L

Count
2.124
46
517

Quant by
Area
Area
Area

Det
Pulse
Pulse
Pulse

Ratio
4,31E-02
9,26E-04
1,05E-02

ISTD
In
In
In

V
Cr
Mn
Fe
Co
Cu

51
52
55
56
59
63

0,719
<0.000
0,815
94,634
0,185
2085,423

ug/L
ug/L
ug/L
ug/dL
ug/L
ug/L

1.427
5.112
1.478
1.620.471
488
3.312.311

Area
Area
Area
Area
Area
Area

Pulse
Pulse
Pulse
Analog
Pulse
Analog

5,41E-02
1,94E-01
5,60E-02
6,14E+01
1,85E-02
1,26E+02

In
In
In
In
In
In

Zn

66

54,905

ug/dL

199.671

Area

Pulse

7,67E+00

In

As
Se

75
78

2,36
110,399

ug/L
ug/L

1.057
5.566

Area
Area

Pulse
Pulse

4,01E-02
2,11E-01

In
In

Mo
Hg

95
202

0,95
3,051

ug/L
ug/L

1.894
1.569

Area
Area

Pulse
Pulse

Pb

208

0,012

ug/dL

1.057

Area

Pulse

4,00E-02

In

with normal pregnancy. This results was consistent with
the finding of a study conducted in Spain that reported
an increase in erythrocyte SOD activity in preeclampsia
patients.(14) The increase may be due to an adaptive
response from oxidative stress. Superoxide radicals
can cause the body to convert non-radicals into radical
products. Excessive radical oxygen species (ROS) can lead
to many negative effects on female reproduction.(15–17)
Thus, preeclampsia induces excessive radical oxygen
species, which is immediately followed by the induction of
endogenous antioxidant enzymes to strengthen the defense
against oxidative injury. However, a study conducted in
Turkey reported no difference in erythrocyte SOD activity
in preeclamptic patients. In contrast, decreased erythrocyte
SOD activity in preeclamptic women compared to controls

74

was also reported.(6,18) The differences in this result could
probably lie in the heterogeneity of this pathology.
Fe in erythrocytes can cause oxidative stress at low
levels (iron deficiency anemia) and also at high levels
(hemochromatosis) through the Fenton reaction.(19)
The negative correlation of SOD activity with iron levels
in erythrocytes can be explained by the fact that Fe is a
contributor to free radicals in intracellular erythrocytes
through the Fenton reaction. Transition metal ions such Fe
and Cu are catalysts for the formation of oxygen radical
species that react with hydrogen peroxide.(20,21) In this
study, the Fe levels of erythrocytes were not examined,
so the amount of free Fe was not known with certainty.
However, some publications also mention a negative
correlation between iron deficiency anemia with erythrocyte

Erythrocyte SOD Activity and Trace Elements in Preeclampsia (Prayudhana S, et al.)
Indones Biomed J. 2025; 17(1): 70-7

DOI: 10.18585/inabj.v17i1.3257

Table 4. Distribution of erythrocyte SOD activity and erythrocyte trace elements.
Variable
Erythrocyte SOD activity (U/mL)

Preeclampsia
a

Erythrocyte SOD activity/Hb (U/g Hb)
Mn (ag/erythrocyte)

a

b

Control

p -value

35.74±7.97

28.9±6.28

0.005*

310.8±83.4

257.88±63.1

0.029*

7.1 (4.3-13.7)

7.6 (4.7-12.4)

0.351

67 (23-82)

75 (24-92)

0.033*

Co (ag/erythrocyte)b

0.15 (0.05-0.61)

0.08(0.02-0.34)

0.027*

b

1.47 (0.08-4.28)

0.93 (0.12-3.39)

0.09

b

57.1(20.4-95.7)

58.5 (24.1-82.4)

1.000

Zn (fg/erythrocyte)b

1.4(0.5-2.0)

1.4(0.5-2.0)

0.850

a

0.46±0.19

0.39±0.09

0.091

a

18.5±4.6

21.7±2.8

0.014*

Cd (ag/erythrocyte)b

0.10 (0.02-0.22)

0.33 (0.01-0.14)

0.006*

b

0.24(0.09-1.57)

0.29(0.09-1.38)

0.273

b

0.03 (0.02-0.1)

0.03 (0.02-0.06)

0.865

9.37±4.67

5.6±2.06

0.003*

Fe (fg/erythrocyte)

b

Ni (ag/erythrocyte)

Cu (ag/erythrocyte)
As (ag/erythrocyte)
Se (ag/erythrocyte)

Hg (ag/erythrocyte)
Tl (ag/erythrocyte)

Pb (ag/erythrocyte)a

Normally distributed data presented in mean±SD, the difference in the mean was calculated by
independent T-test. bNot normally distributed data presented in median (minimum-maximum value),
the median difference is calculated by the Mann-Whitney U test. *Significant if p<0.05.
a

SOD activity.(22) Iron deficiency anemia could induce
oxidative stress, which in turn responded by erythrocytes to
increase antioxidant activity.(23,24)
In this study, it was found that the Se level of
preeclampsia erythrocytes was lower than controls. Levels
of Se in erythrocytes could have a protective effect on

Table 5. Correlation test of erythrocyte trace elements with
erythrocyte SOD.
Trace Elements

Correlation
coefficient (r)

p -value

-0.172

0.289

b

-0.370

0.019*

b

0.059

0.717

b

0.247

0.152

b

0.023

0.886

b

-0.173

0.285

a

-0.124

0.445

a

-0.115

0.481

Cd (ag/erythrocyte)

b

0.163

0.407

Hg (ag/erythrocyte)

b

-0.295

0.065

b

-0.011

0.957

a

-0.108

0.508

Mn (ag/erythrocyte)
Fe (fg/erythrocyte)

Co (ag/erythrocyte)
Ni (ag/erythrocyte)

Cu (ag/erythrocyte)
Zn (fg/erythrocyte)

As (ag/erythrocyte)
Se (ag/erythrocyte)

Tl (ag/erythrocyte)

Pb (ag/erythrocyte)

b

Normally distributed data, tested using the Pearson correlation
test. bNot normally distributed data, tested using the Spearman
correlation test. *Significant if p<0.05.
a

preeclampsia.(25) Se acts as a cofactor for the antioxidant
glutathione peroxidase, which also fights free radicals.
The antioxidant system of erythrocytes is not only SOD
but several other enzymes were not included in this
study. Decrease Se could be accompanied by antioxidant
glutathione peroxidase in response to free radicals.(25)
There was a significant difference in the levels of Cd,
Co, and Pb in erythrocytes compared to controls found in the
current study. Although Cd is not the catalytic metal in the
Fenton reaction, it induces oxidative stress in various animal
models through indirect mechanisms.(21) The degree of
Cd-induced oxidative stress depends on the dose, duration,
and frequency of Cd exposure. Serum availability under
experimental conditions, cell type, and antioxidant capacity,
as well as Cd speciation, are important determinants.(26)
At the cellular level, Cd-induced oxidative stress causes
oxidative damage or activates signal transduction pathways
to initiate a defensive response.(25) The role of Cd for
cellular function in humans is still largely unknown. Still,
Cd can induce oxidative stress response via metal transfer
cellular redox status, decreased redox scavenger capabilities,
inhibition of antioxidant enzymes, and inhibition of the
electron transport chain resulting in mitochondrial damage.
(27,28) A study in Boston on 1274 pregnant women with,
115 of them preeclampsia, it was found that Cd levels in
erythrocytes were increased.(25) Population differences
related to the environment, such as pollution and food, can
influence this.
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The Indonesian Biomedical Journal, Vol.17, No.1, February 2025, p.1-108

Co and Pb are toxic heavy metals that could be
linked to preeclampsia. Erythrocytes’ Co and Pb levels of
preeclampsia in this study were found to be significantly
higher than controls. However, previous research conducted
in Boston found no differences in preeclamptic women's
erythrocytes’ Pb compared to controls.(25) However, in
developing countries such as Congo, it was found that Co
and Pb in urine were higher in preeclamptic women.(29)
Concentration of trace elements such as Cd, Hg, Pb,
and Se was higher in erythrocytes than in plasma for maternal
and umbilical cord blood samples.(30) Concentrations of
Hg, Pb, and Se in maternal erythrocytes strongly correlated
with their levels in the umbilical erythrocyte. In this study,
there was no find significant differences in the levels of other
trace elements: Ni, As, Hg, and Tl. Cr, V, and Mo levels
were also not detected. Seeing the role of toxic metals such
as Cd and Pb, N-Acetylcysteine therapy has the potential
to be given to prevent preeclampsia. N-acetylcysteine is
a derivative of cysteine, an amino acid, and can function
as a chelator to remove metals, including Hg, Cd, Cr, As,
and Pb.(31) However, N-Acetylcysteine does not appear to
cause increased excretion of essential metals such as Fe, Zn,
Cu, and Ca.(31)
In current study, only the status of antioxidants and
trace elements were examined between both groups and did
not directly describe the antioxidant stress that occurred.
For further study, it would be better to examine NO levels
in plasma or erythrocytes to help describe the maternal
endothelial dysfunction in preeclampsia. Larger scale of
research also needed to reduce the bias.

Conclusion

This study demonstrated significant differences in
erythrocyte trace element levels between preeclampsia
and normotensive patients. Specifically, Fe, Se, and Cd
levels were lower in the preeclampsia group, while Co
and Pb levels were higher. These findings suggest that
alterations in erythrocyte trace element levels may serve as
potential biomarkers for the prediction or management of
preeclampsia.

Print ISSN: 2085-3297, Online ISSN: 2355-9179

Authors Contribution

All authors were invoved in the study design and conception.
SP and NW collected the data of the study. SP performed the
analysis, interpretation of data and wrote the original draft of
the manuscript. RI, YP, YBS, DP and NW revised the paper
and had primary responsibility for the final content. All
authors agreed to the published version of the manuscript.

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Acknowledgments

The author would like to express gratitude to all the patients
who participated in this study. Gratitude also given to PT.
Prodia Widayahusada Tbk. for the help in this research.

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