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Journal of
Trace Elements
Trace Elements
in Medicine and Biology
Journal of Trace Elements in Medicine and Biology 18 (2004) 163– 171
PATHOBIOCHEMISTRY
Serum trace element levels and the complexity of inter-element relations in
patients with Parkinson’s disease
Muralidhar L. Hegde
a
, Ponnuswamy Shanmugavelu
b
, Bhuma Vengamma
c
,
T.S. Sathyanarayana Rao
d
, Rani B. Menon
b
, Ranganath V. Rao
b
,
K.S. Jagannatha Rao
a,
a
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570020, India
b
Analytical Control Section, Chemical Engineering and Technology Group, Bhabha Atomic Research Centre,
Mumbai 400085, India
c
Department of Neurology, Shri Venkateswara Institute of Medical Sciences, Tirupati 517502, India
d
Department of Psychiatry, J.S.S. Medical College and Hospital, Mysore 570004, India
Received 12 April 2004; accepted 14 September 2004
Abstract
Trace elements have been postulated to play a role in Parkinson’s disease (PD). In order to elucidate whether
changes in the serum levels of trace elements reflect the progression of PD, we assessed serum levels of 12 elements (Na,
K, Fe, Al, Cu, Zn, Ca, Mg, Mn, Si, P and S) in early PD, severe PD and normal subjects, using inductively coupled
plasma atomic emission spectrometry. The concentrations in mmol/ml, the relative mole percentage distribution and
inter-element relations were computed. Statistical analysis of these data showed a definite pattern of variation among
certain elements in early and severe PD compared to controls. In both early and severe PD serum, Al and S
concentrations were significantly decreased (po0:05) compared to the controls. Fe (po0:01) and Zn (po0:05)
concentrations were significantly lower in severe PD, while K, Mg, Cu (po0:01) and P (po0:05) concentrations were
higher in early and severe PD compared to the controls. The data revealed an imbalance in the inter-element relations
in both early and severe PD serum compared to controls, as shown by the direct and inverse correlations. These results
suggest a disturbance in the element homeostasis during the progression of PD.
r2004 Elsevier GmbH All rights reserved.
Keywords: Parkinson’s disease; Element homeostasis; Inter-element relation; Serum; Early PD; Severe PD
Introduction
Trace elements at optimum biological levels are
required for numerous metabolic and physiological
processes in the human body. Elements like Na, K,
Mg, Ca and P serve as structural components of tissues
and as constituents of the body fluids and are therefore
essential for the functioning of the cells [1]. Imbalances
in the optimum levels of these elements as well as trace
metals such as Fe, Cu, Zn and Al may adversely affect
biological processes and are associated with many
neurological diseases [2–7].
The pathogenesis of neuronal degeneration in the pars
compacta of substantia nigra in patients with Parkin-
son’s disease (PD) is still not clearly known. Several
studies have suggested the presence of oxidative stress in
substantia nigra of PD patients [8–14]. An increase in Fe
and other paramagnetic trace metals in substantia nigra
could hypothetically elicit oxidative processes.
ARTICLE IN PRESS
www.elsevier.de/jtemb
0946-672X/$ - see front matter r2004 Elsevier GmbH All rights reserved.
doi:10.1016/j.jtemb.2004.09.003
Corresponding author. Fax: +091 821 2517233.
E-mail address: kjr4n@yahoo.com (K.S. Jagannatha Rao).
Limited data is available concerning the levels of
metals in serum during pathological conditions of PD.
Studies have suggested that levels of transition metals
like Zn, Cu and Fe in serum do not play a role as risk
factor indicators for PD [15]. Moreover, most of the
available information is limited to a few selected
elements [16,17] and there is no study examining inter-
element relations with regard to the severity of PD. The
aim of the present study was to assess the serum levels of
12 elements (Na, K, Fe, Al, Cu, Zn, Ca, Mg, Mn, Si, P
and S) in patients with early and severe PD compared
with a control population, and also to understand the
possible relevance of inter-element relations for the
progression of PD.
Patients and methods
Patients
We assessed the serum levels of 12 elements in early
and severe PD patients in comparison with controls.
Blood samples were collected from 52 patients with PD
(27 early and 25 severe PD) recruited among the
outpatients attended in the Neurology Departments of
two urban hospitals (Sri Venkateswara Institute of
Medical Science and J.S.S. Medical Hospital, India).
The PD patient group was graded into early PD and
severe PD according to clinical severity of the disease.
All patients met the commonly accepted diagnostic
criteria for PD [18] and were evaluated by the Unified
Parkinson’s Disease Rating Scale (UPDRS) [19] and the
Hoehn and Yahr staging [20]. The first stage of the
Hoehn and Yahr staging of PD was considered as early
PD, while the latter stages of Hoehn and Yahr staging
were assigned to severe PD. 14 of the 27 early PD
patients were untreated, the other 13 patients were
treated with one or a combination of antiparkinsonian
drugs such as levodopa (11 cases) and anticholinergics (2
cases). Of the 25 severe PD patients, 6 were untreated,
and 19 were treated with antiparkinsonian drugs—a
single drug or a combination—including levodopa (18
cases) and anticholinergics (3 cases). Cases with
occupational exposures to Fe and Mn were excluded
from the study. The main clinical features of the PD
patients and controls are shown in Table 1.
The control group comprised 25 volunteers with no
significant illnesses or medications for at least 3 months
before the time of blood collection. Both the control and
the PD groups were assessed by a neurologist and a
psychiatrist.
The following exclusion criteria applied to both PD
patients and controls [21,22]: (a) ethanol intake higher
than 80 g/day during the last 6 months; (b) previous
history of chronic hepatopathy or diseases causing
malabsorption; (c) previous history of severe systemic
disease; (d) atypical dietary habits (diets constituted
exclusively by one type of foodstuff such as vegetables,
fruits, and meat, or other special diets because of
religious reasons, etc.); (e) previous blood transfusions,
anemia and polycytemia; (f) intake of supplements of
Fe, Cu, Al, Zn or chelating agents; (g) therapy with
chlorotiazides, adrenocorticotropic hormone (ACTH)
or steroids; (h) acute infectious disorders, traumatisms
or surgery in the last 6 months; and (i) haemolytic
anemia.
Ethical approval for the collection of blood samples
from PD and control patients was obtained from the
research ethical committee of the J.S.S. Medical College
and Hospital and Sri Venkateswara Institute of Medical
Science, India. A written consent was obtained from the
patients/carers prior to the collection of blood samples.
Precautions to avoid cross contaminations during
sample collection and storage
10 ml of venous blood was collected from each PD or
control patient using intravenous canula to avoid iron
contamination, and serum was separated by centrifuga-
tion. The serum was frozen at 20 1C and protected
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Table 1. Clinical features of the PD patients and the control group
Early PD (n¼27) Severe PD (n¼25) Control (n¼25)
Age (years) 57.1575.2 59.3073.9 55.476.4
Sex 13 F/14 M 11 F/14 M 12 F/13 M
Duration of PD (years) 2.770.9 7.071.4
Hoehn and Yahr stage 1st stage 2nd stage onwards
Scores of Unified PD Rating Scale:
Total (items 1–31) 23.1711.4 57.6715.6
ADL
a
subscale (items 5–17) 975.2 22.377.3
Motor subscale (items 18–31) 17.875.8 29.7713.6
Data of quantitative variables are expressed as mean7standard deviation.
a
ADL: activities of daily living.
M.L. Hegde et al. / Journal of Trace Elements in Medicine and Biology 18 (2004) 163–171164
from exposure to light until analysis. Blood collection
and serum separation were carried out in dust free
environments. All tubes used were polypropylene, no
glass material was used to prevent Al and Si contam-
inations. All precautions to eliminate metal contamina-
tion during blood collection and storage were taken in
accordance with National Committee for Clinical
Laboratory Standards (NCCLS) criteria [23].
Instrumentation and element analysis
The element analysis was carried out using inductively
coupled plasma atomic emission spectrometry (ICP-
AES) (JY 70, Jobin Yvon, France), either by sequential
or simultaneous mode depending on the elements to be
analyzed. All dilutions were made with ultra pure Milli
Q water (18 MOresistance) in dust free environment.
For optimization of the ICP-AES method, lines were
selected and detection limits evaluated for each element.
The lines were chosen for each element in a way to
obtain minimum interferences from other elements. The
wavelengths used and the detection limits of the
elements are summarized in Table 2. Quality control
of the analyses was performed by analyzing a serum
matrix matched multi-element synthetic standard
and certified standard reference material (Bovine
liver 1577a) obtained from the National Bureau of
Standards, USA [24].
Data analysis
The element concentrations are expressed in mmol/ml
as mean7standard deviation and range of values. The
mole percentage (element concentration in mol%=ele-
ment concentration (mmol/ml) 100/total element con-
centration (mmol/ml) of all analyzed elements in each
sample) was calculated for the analyzed elements and
the relative distribution based on the mole percentage
was computed. Mole percentage calculations are essen-
tial to understand the relative distribution of each
element in relation to other elements in a biological
matrix. In addition, a normalization of the data of
different samples is achieved in order to obtain clear
inter-element relations. Element to element ratios and
correlations were calculated based on the mole percen-
tages to find possible element inter-relations (direct and
inverse) in control and PD serum samples.
All statistical calculations such as inter-relations,
correlation coefficients, and t-tests were carried out
using Microsoft Excel 2000 and ‘graph pad prism’
software.
Results
Element concentrations
Element concentrations for control, early PD and
severe PD serum samples are given in Table 3. The data
are presented in mmol concentrations in order to
calculate mole ratios of the elements and to determine
inter-element correlations. The difference in percent in
serum element concentrations between early or severe
PD patients and controls, as well as between early and
severe PD patients are presented in Table 4. The results
clearly show that serum levels of K, Mg, Cu and P were
statistically significantly higher (po0:01) in both early
and severe PD compared to the controls. Serum S and
Al concentrations were significantly lower (po0:05) in
both early and severe PD, while Fe and Zn concentra-
tions were decreased significantly (po0:01) only in
severe PD compared to controls, which may reflect the
severity of PD. Interestingly, in early PD serum samples,
the concentrations of P, Cu, K and Ca were higher than
in control and severe PD samples. However, there was
only a marginal increase in the total concentration
(mmol/ml) of the measured elements in early and severe
PD serum compared to the controls. There was no
correlation of these values with age at onset, sex or
antiparkinsonian therapy. These findings are in agree-
ment with previous studies [15,17].
The element concentrations determined in the present
study in serum of control human subjects were
compared with reference values from the ‘Handbook
on metals in clinical and analytical chemistry’ [25] and
from the study of Muniz et al. [26] (Table 3). The values
matched for most of the elements, except for K, Al and
Zn, where larger variations were observed. Normal
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Table 2. Inductively coupled plasma atomic emission spec-
trometry: wavelenghts and detection limits
Element Wavelength (nm) Detection limit
a
mg/ml mmol/ml
Na 588.995 0.03 0.00130
K 766.49 0.06 0.00153
S 182.98 0.05 0.00156
P 213.618 0.05 0.00162
Ca 393.366 0.002 0.00005
Mg 279.806 0.001 0.00004
Cu 224.7 0.002 0.00003
Zn 213.856 0.002 0.00003
Fe 259.94 0.005 0.00009
Al 396.152 0.002 0.00007
Mn 257.61 0.001 0.00002
Si 251.611 0.08 0.00285
a
The detection limits were calculated by running a multi-element
standard solution containing 500 ng/ml of each element.
M.L. Hegde et al. / Journal of Trace Elements in Medicine and Biology 18 (2004) 163–171 165
values for Al in serum samples are a contentious issue.
Even though it has been agreed that Al levels should be
lower than 0.005 mg/ml in control human serum, in
many studies values of around 0.010–0.020 mg/ml have
been reported. The Al level in control human serum in
the present investigation was 0.016 mg/ml.
Relative mole percentages
To elucidate the inter-element relations within the
data sets of the control, early PD and severe PD
samples, the concentrations (in mmol/ml) were normal-
ized by calculating the mole percentage for each element
in a sample. The relative distribution is presented in Fig.
1. The mole percentage data show that levels of Al, Fe
and S levels were higher in control serum compared to
early and severe PD samples. Na and K were higher in
both PD groups than in controls. Regarding the divalent
elements, mole percentages of Mg and Cu were higher,
while Zn values were lower in early and severe PD serum
compared to the controls. No significant difference was
observed for Ca.
Inter-element correlations and mole percent ratios
The inter-element correlations for the analyzed
elements in control, early PD and severe PD samples
showed a distinct pattern of direct and inverse correla-
tions for selected elements. The correlation co-efficients
and the statistical confidence levels at which the
correlations were determined are given in Table 5.Na
was inversely correlated (rX0.95) with S in all groups.
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Table 3. Element concentrations (in mmol/ml7standard deviation) in control, early and severe PD serum
Element Reference values from
Ref. [25] or [26]*
Control Early PD Severe PD
Na 139.2* (134.8–147.8) 135.474.1 (126.5–141.3) 142.6711.4
(125.0–164.5)
142.979.8 (127.2–168.5)
K (4.09–4.48)* 3.5470.6 (2.4–4.9) 4.4670.4 (3.3–5.4) 3.7970.4 (2.8–4.7)
S Not available 36.673.7 (31.1–44.5) 32.075.0 (25.3–45.6) 31.173.3 (26.5–38.0)
P 3.56 3.270.4 (2.3–4.0) 4.1270.9 (2.7–6.8) 3.6570.5 (2.8–4.5)
Ca 2.35 (2.2–2.6) 2.270.2 (1.8–2.5) 2.4170.3 (1.8–3.0) 2.2370.2 (2.18–2.69)
Mg (0.6–1.07) 0.970.09 (0.78–1.1) 1.0570.1 (0.82–1.3) 1.0570.08 (0.86–1.19)
Cu 0.017 0.01470.003
(0.009–0.019)
0.02270.008
(0.007–0.035)
0.0270.006
(0.011–0.035)
Zn 0.013 0.00970.001
(0.006–0.01)
0.00870.002
(0.006–0.012)
0.00770.001
(0.005–0.009)
Fe (0.012–0.030) 0.02370.009
(0.016–0.047)
0.0270.004 (0.01–0.028) 0.01770.007
(0.004–0.035)
Al
a
o0.2 0.5970.04 (0.4–0.68) 0.4570.05 (0.34–0.5) 0.3770.1 (0.29–0.5)
Mn Not available oDL (DL:0.00002) 0.00170.0002
(0.0005–0.034)
0.00170.0002
(0.0004–0.045)
Si Not available oDL (DL: 0.00285) 0.03270.01 (0.002–0.06) 0.00970.002
(0.004–0.014)
Total 181.876.3 (170.3–195.5) 186.7715.9
(162.7–218.4)
184.8710.5
(168.1–205.9)
DL: detection limit.
Values in parentheses indicate the range. Reference values of elements (in mmol/ml) in control human serum from Ref. [25] or [26] (the latter marked
with an asterisk) are given in the second column for comparison.
a
In nmol/ml.
Table 4. Differences in percent of element concentrations
between control and early or severe PD, and between early and
severe PD.+and signs indicate increasing or decreasing
trends
Metals Control/early PD Control/severe PD Early/severe PD
Na +5.3
a
+5.6
a
+0.2
K +26.0
a
+7.2
b
15.0
a
S12.6
a
15.1
a
2.8
b
P +30.0
b
+15.4
a
11.4
b
Ca +8.7
b
+0.6 7.5
b
Mg +16.2
a
+16.2
a
0.0
Cu +63.2
a
+62.1
a
9.1
b
Zn 8.4
a
19.4
b
12.5
b
Fe 13.9
b
29.5
a
15.0
a
Al 23.7
a
37.3
a
17.8
a
Statistical significance, a: po0:01;b: po0:05:
M.L. Hegde et al. / Journal of Trace Elements in Medicine and Biology 18 (2004) 163–171166
This correlation was also found in our previous
studies on cerebrospinal fluid of Alzheimer’s
patients [27]. Na was directly correlated with K and
Al in the control group, but showed a tendency
towards inverse correlation in both early and severe
PD groups. K was inversely correlated with S and
Zn, and S with Al in the control group, but
showed a tendency towards direct correlation in both
PD groups. A direct correlation was found between S
and Fe in the control group, and between Cu and Zn in
the severe PD group.
The data were further analyzed in terms of element-
to-element mole percentage ratios in control, early and
severe PD serum. The ratios were calculated in order to
understand the inter-relations of elements in biological
systems [24,27]. The ratios Na/K, Na/Cu, Fe/Cu, S/Mg,
and S/Cu were significantly decreased in early and
severe PD serum compared to the controls, while the
ratios K/Al, S/Al, Mg/Al, P/Al, K/Fe, K/Zn and Cu/Zn
showed an increasing trend in PD serum compared to
the controls. Only moderate differences were observed
for other element ratios.
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1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0
0.000
0.005
0.010
Control Early PD Severe PD
1
2
20
40
60
80
Co
n
Ear
0.0000
0.0001
0.0002
0.0003
0.0004
Micromole %
Al
Na S K P Ca Mg Cu Zn Fe Al
Micromole % of Elements
Fig. 1. Comparison of relative mole percentages of elements in control, early and severe PD human serum samples.
Table 5. Comparison of inter-element relations between control, early PD and severe PD serum samples
Correlation between elements Correlation co-efficient
1 2 Control (n=25) Early PD (n=27) Severe PD (n=25)
Na S 0.99* 0.95* 0.95*
Na Ca 0.46** 0.0 0.59**
Na K 0.47** 0.32 0.22
Na Al 0.49** 0.1 0.05
KS 0.51** 0.11 0.36
KZn0.42** 0.42** 0.48**
KCa0.29 0.49** 0.36
SAl0.49** 0.09 0.05
S Fe 0.40** 0.03 0.12
Cu Zn 0.09 0.29 0.49**
PFe0.58** 0.12 0.39
Confidence levels: *499.9%, **495%. At 99.9% and 95% confidence levels, the expected correlation co-efficients for a sample size of 25 are 0.613
and 0.396 respectively. signs indicate an inverse correlation.
M.L. Hegde et al. / Journal of Trace Elements in Medicine and Biology 18 (2004) 163–171 167
Discussion and conclusions
In the last decade, there has been an increasing
interest for the possible role of metals in the pathogen-
esis of PD [15,28–30]. Substantial information is
available on the trace metal distribution in brains of
controls [27,31] and patients with neurodegenerative
diseases like Parkinson’s, Alzheimer’s and Huntington
disease [27,29,32,33]. Previous investigations [34] have
shown an increase in Fe and Zn concentrations in the
substantia nigra, lateral putamen and caudate nucleus in
PD brain. However, limited data is available on some
selected elements in serum of PD affected patients.
Moreover, there has been a controversy regarding the
Zn and Cu levels in PD serum. Abbot et al. and Pan et
al. [35,36] reported decreased serum Zn concentrations
in PD serum, while Jimenez et al. [16] found no
significant difference in Zn concentrations in PD serum
compared to controls. The present study shows
decreased Zn levels in both early and severe PD serum,
which is in agreement with Abbot et al. and Pan et al.
[35,36]. Serum Cu concentrations were found to be
normal in previous studies [16,37,38], or decreased in
another study [36]. In contrast, in the present study,
increased Cu concentrations were observed in both early
and severe PD serum (445–65%) compared to the
controls.
Furthermore, Jimenez-Jimenez et al. [15] reported
that the serum levels of Fe and Mn did not differ
significantly between PD patients and controls. How-
ever, other studies [35,39] reported decreased serum Fe
levels. In the present study, a significant decrease in Fe
and a moderate increase in Mn concentrations were
observed in PD serum compared to control serum.
Interestingly, Fe showed a gradual decreasing trend with
the severity of PD. The Fe concentration was lower by
14% and 30% in early and severe PD, respectively,
compared to the controls.
There are no previous studies on serum levels of
elements like Na, K, S, P, Ca, Mg, Si and Al. In the
present study, mole percentage ratios and the correla-
tion patterns of the elements indicated that there is an
imbalance in the element-to-element inter-relations in
serum of PD affected individuals (Table 5).
There has been a controversy regarding metal levels in
PD serum and the possible role of metals as risk factors
for PD. It is not clear whether the alterations in metal
homeostasis is a cause or consequence in the pathology
of the disease. So far, there is no detailed or
comprehensive database on metal homeostasis and
inter-relations. The available reports only indicate
changes in the levels of a few elements, but fall short
to correlate the element-to-element inter-relation pat-
tern with the progression of the disease. In this
perspective, the present study provides a comprehensive
database on concentrations of 12 elements (the majority
being essential elements) in PD serum in comparison
with a control group.
There is limited information concerning a correlation
of the element homeostasis in brain, cerebrospinal fluid
(CSF), serum and other vital organs. Pall et al. [38] and
Pan et al. [36] reported increased Cu levels in the CSF of
patients with PD, the former group further suggesting
that the concentration of this metal might be elevated in
the brain as well. However, several studies [30,40] found
decreased levels of Cu and increased levels of Fe and Zn
in the substantia nigra, lateral putamen and caudate
nucleus in PD brain. The authors related the increased
Zn concentration to an attempt of protection against
oxidative stress arising from the increased Fe level. An
inverse relation between Fe and Cu (in liver) [41] and a
direct relation between Fe and S as well as Zn has been
found [28]. Thus the increased Zn levels and decreased
Cu levels in PD brain may be causally related to the
increase in Fe concentration. CSF Zn levels were found
to be decreased in a study conducted by Jimenez-
Jimenez et al. [15]. However, it is not clear, whether the
source for increased Fe and Zn levels in the brain is
serum or CSF. Furthermore, there is a need to under-
stand the primary factor triggering the element imbal-
ance in the body and its consequences. Trace metals play
an important role in neuronal functions. The levels of
trace metals in serum may be related to the levels in
brain with reference to essential elements, but not
regarding non-essential elements or metals causing toxic
effects. The essential metals are able cross the blood
brain barrier (BBB) by selective uptake mechanisms.
However, non-essential or harmful metals can also cross
the BBB by replacing essential metals in carrier proteins
like transferrin.
How or why a specific increase in the total Fe content
of substantia nigra should occur in PD is not under-
stood. According to Lenders et al. [42], the Fe uptake
across the BBB into the brain is significantly higher in
PD patients than in matched controls (PET study). They
suggested that this elevated Fe content in brain could be
related to an increased transferrin receptor formation in
PD. Fe is transported from blood to brain by the carrier
protein transferrin. Fe and transferrin are transported
through the BBB by means of a transferrin receptor
mediated transcytosis [43–45]. In another study it has
also been argued that the increased Fe levels correlated
with the severity of neuropathological changes in PD are
presumably due to an increased transport through the
BBB [7]. Thus, two likely pathways for an increased Fe
and Al uptake in dopaminergic neurons of substantia
nigra may be the increase in transferrin receptor protein
in PD brain and the non-specific pathological influx
from other regions of the brain [30]. Al is known to be
co-transported with the Fe-transferrin complex in
neurological disorders [34]. In normal brain, Fe and
Al compete for the transport across the BBB [27] while
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M.L. Hegde et al. / Journal of Trace Elements in Medicine and Biology 18 (2004) 163–171168
in Alzheimer’s disease, Fe and Al co-transport [34]. This
differential mechanism is puzzling.
Fe exists in the brain in different complex forms, not
all of them being capable of catalyzing oxidative stress.
The majority of Fe is bound to ferritin and thus
inactivated under normal physiological conditions. The
biosynthesis of ferritin is controlled by the availability of
Fe [46]. Glial Fe is mainly stored as ferric iron in ferritin,
while neuronal Fe is predominantly bound to neurome-
lanin [7]. The potential toxicity of the increased Fe load
in substantia nigra in PD is therefore determined by the
extent of the binding of Fe to ferritin and other moieties.
In PD, the increased total Fe level in substantia nigra
was not associated with a compensatory increase in
ferritin; on the contrary, the brain ferritin immuno-
reactivity was decreased [47]. Hence the increased Fe
load in PD may exceed the storage capacity of available
ferritin, leading to an excess of reactive Fe, driving free
radical generation [30]. This hypothesis is supported by
an increase in basal lipid peroxidation found in
substantia nigra in PD [48]. Thus, an iron overload
and an imbalance in other redox metal levels may induce
the progressive degeneration of nigrostriatal neurons by
facilitating the formation of reactive intermediates,
including reactive oxygen species, and of cytotoxic
protein aggregates [7,49].
We believe that—regardless whether metals are
primary risk factors or imbalances are consequences of
pathological mechanisms—a moderate change in a
single metal ion concentration will upset the whole
element homeostasis, resulting in significant imbalances
in element levels in the whole system (serum, CSF and
brain). The effect of an increase or decrease in a single
element concentration is not restricted to this element
alone, but the total element distribution pattern in the
system will be affected. The results of the comparison of
trace elements in serum of PD patients and control
subjects in the present study showed that a disturbance
in element homeostasis and inter-element relations
occurs in serum during progression of PD.
Acknowledgements
The authors thank Dr. V. Prakash, Director, CFTRI,
Shri B. Bhattacharjee, Director, BARC, Mumbai, Shri.
T.K. Bera, Project Manager, BARC for their encour-
agement, as well as Dr. Luigi Zecca, CNR-Institute,
Italy for his suggestions. We thank the clinicians and
nurses at the SVIMS and JSS Hospitals for their
assistance in collecting the blood samples. We also
thank the CSIR-CNR project on toxicity of metals in
human brain for financial support. MLH thanks the
Council of Scientific and Industrial Research, New
Delhi for his Senior Research Fellowship.
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