Dietary Intakes Influence on Metallomic Distribution in Vital Organs

and Their Implications

Solomon W. Leung

, Brad Williams

and James C. Lai

Civil and Environmental Engineering Department and Measurement and Control Research Center, Idaho State University,

Pocatello, Idaho, 83209, USA

Civil and Environmental Engineering Department, Idaho State University, Pocatello, Idaho, 83209, USA

Biomedical and Pharmaceutical Sciences Department, Idaho State University, Pocatello, ID 82309 USA

Keywords: Elements Distribution, Mn, Nutrition Intake, Vital Organs

Abstract: The intake and concentration of metals and electrolytes in our diet are believed to be affecting our general

health, in particular, the proper functions of vital organs. For example, in addition to other genetic and

environmental factors, consuming water with high alkalinity for a prolonged time is suspected of leading to

diseases such as kidney stones. There is evidence that elemental accumulation due to excessive metal

intakes would lead to organ failure. This study is an extensive investigation of metallomic distribution in

Wistar Rats after they have consumed 30 different elements (including heavy metals and electrolytes) via

dietary intakes throughout their lifespan (from 5 to 750 days). In this study, the distributions of these

elements in various vital organs such as heart, kidney, lung, spleen, liver, pituitary, and uterus over time

were analyzed. In addition, how heavy metal supplement, such as Mn, influenced the elemental

accumulations inside the organs was also conducted. This study has high impact to our understanding of

how the environment would affect our well beings. This study would provide insights on how our diet

would affect the accumulations of unwanted elements, such as heavy metals, in our vital organs. The results

may also help researchers and health practitioner to identify possible links between daily diet and associated

diseases inside the vital organs.

1 INTRODUCTION

Since the era of industrial evolution, living

conditions for human have improved drastically;

with the consequence of better living conditions and

less physical activities, we are facing other aspects

of health issues such as obesity and hyper immunity

responses (allergy). In modern living, considerable

attention has been paid to dietary intake or

supplement due to health concerns. On the other

hand, involuntarily consumption of unwanted

chemicals and preservatives via processed foods and

polluted water is also possible. One such example

would be consumption of drinking water source that

is laden with soluble ions and heavy metals. This

occurs quite frequently for those that are living in

rural areas with no proper treatment system for their

drinking water in developing countries.

Attempts in understanding the homeostasis of

different elements in brain and other major organs

fell short significantly due to the vast complexity of

the mechanisms involved (Pardridge, 2003). What

cause this complexity are the multiple factors that

can affect the dynamics of biological functions. For

examples, an element of different compounds

(chloride versus phosphate) would have various

uptake rates (Anderson et al., 2008) and the uptake

rate of elements in solution by the digestive system

was proven to be faster than in food stuffs.

Elemental accumulations are not solely related to

exposure but likely have more to do with

impairment of the relevant homeostasis mechanism

(Bolognin et al., 2009); conversely, a known Cu

deficient sample of mice were able to be revised by

supplementation of Cu in drinking water (Bayer et

al., 2003). In addition, larger sample size is needed

to observe statistical significance in the small

changes over lifetime exposure (Maynard et al.,

2009). Such constraint creates a vast financial and

operational obstacle to conduct research, and the

hurdle is more difficult if human subject is involved.

Currently, the understanding of homeostasis

mechanisms for accumulation and control of

individual element in our body is very limited,

W. Leung, S., Williams, B. and C. Lai, J.

Dietary Intakes Inﬂuence on Metallomic Distribution in Vital Organs and Their Implications.

DOI: 10.5220/0008654100300036

In Proceedings of the International Conference on Future Environment Pollution and Prevention (ICFEPP 2019), pages 30-36

ISBN: 978-989-758-394-0

hence, the influence of similar elements to each

other is practically non-existent. However, the result

of Zn replacing Cu in a competitive homeostasis

mechanism in rat’s brain was recently reported by

Maynard et al. (2009). Therefore, it can be

concluded that our understanding of elemental

homeostasis mechanisms in our body systems is still

in the beginning stage, and the opportunities for

more research and development are immensely

available.

There are chemicals (vitamins, for example) and

elements and trace elements that we need to

maintain proper bodily functions; in this study, we

focused on the essence of major and selected trace

elements and how these elements accumulated in our

major organs. The major organs are: heart, kidney,

lung, spleen, liver, pituitary, and uterus. Information

matrices of these 30 different elements (including

heavy metals and some electrolytes) that were fed to

rats as part of a regular diet were obtained from the

seven major organs and analyzed. Furthermore, we

fed the rats with various concentrations of Mn (as a

surrogate of heavy metal) and observed how these

30 elemental accumulations in the vital organs were

affected by the different consumptions of Mn in the

diet as an adult (120 days).

2 EXPERIMENTS AND

PROCEDURES

The 30 elements included in this study were: Al, As,

Ba, Br, Ca, Cd, Cl, Co, Cr, Cu, F, Fe, Hg, I, K, La,

Mg, Mn, Mo, Na, Rb, S, Sb, Sc, Se, Si, Sm, Sr, V,

and Zn. Analytical measurements of the elements

from the organs of adult (120 days) Wistar rats and

diet pellets that were used to feed the rats were

reported in a previous paper (Wright et al.). Table 1

lists the elements of the rat food pellet detectable by

Instrumental Neutron Activation Analysis (INAA),

elements that were from the 30 interested elements

but not listed in Table 1 were not detectable by

INAA due to low concentration. All values listed

are means ± standard deviations of the 20 detectable

elements. ND indicates not detectable, and values in

brackets are the maximum elemental concentrations

present in the pellet diet.

The main analysis for this paper is to compare

elemental accumulations in the said organs above in

relations to control adult rats and Mn-treated adult

rats. The Mn dosages of control and three different

adult groups are listed as follows:

1. Control samples taken from 120- days-old

adult female Wistar Rat.

2. Group A adult with life-long manganese

treatment with 1 mg/ml MnCl

·4H

O in drinking

water.

3. Group B adult with life-long manganese

treatment with 10 mg/ml MnCl

·4H

O in drinking

water.

4. Group C adult with life-long manganese

treatment with 20 mg/ml MnCl

·4H

O in drinking

water.

Table 1: Elemental concentration of rat food pellet

Element

Concentration

mg /g

6.393

1.68

mg /g

2.305

0.485

mg /g

0.25

0.051

mg /g

5.362

0.951

mg /g

1.168

0.322

mg /g

1.475

0.32

gg

98.06

8.05

gg

10.57

2.26

gg

0.2

0.04

gg

1.5

0.44

gg

7.21

2.12

gg

ND(5.0)

gg

ND(.25)

gg

ND(.5)

gg

49.34

8.65

gg

2.8

0.45

gg

ND(.25)

gg

12.73

2.61

gg

ND(.5)

gg

47.73

4.11

3 RESULTS

3.1 Heart

Mercury (Hg) is most drastically impacted by Mn

treatment. Hg content has increased about 18 times

from the control concentration. Along with the

increase in Hg, there is higher Hg concentration with

higher dosages of Mn treatment. Hg concentration

Dietary Intakes Inﬂuence on Metallomic Distribution in Vital Organs and Their Implications

in the heart is showing an impact with prolonged Mn

intake. Molybdenum (Mo) also had a large increase

in concentration from control levels. An interesting

effect is with Calcium (Ca). From the A dosage

level Ca increased almost 100% but then on the B

dosage level Ca slightly decreased. Then Ca

increased again on the C dosage level.

The impact of Mn on Hg is an important point to

highlight. Mn has been known to be present in

drinking water and also used to treat drinking water

that would lead to Mn ingestion. There are known

harmful elements that will greatly increase in

accumulation in the body by Mn ingestion.

Increased Hg in the heart is a concern also because

Hg is a well-known neurotoxin. Its impact on the

heart directly may not be clear but there are other

known adverse effects on the brain, nervous system,

and kidneys.

In general, above normal elemental accumulation

in the heart can lead to functional loss or heart

failure. The risk of heart failure by increased

accumulation of heavy metal in itself is worth

additional study and investigation. From this

analysis, increases in heavy metal’s presence that are

induced by Hg may contribute to heart failure.

-5

A B C

Mn Treatment Dosage

Figure 1: Results of heart with Mn treatment for Group A,

B, and C as compared with control.

3.2 Kidney

For Mn treatment, the kidney showed increases in

Mn but also showed decreases in V. Mo increased

for treatment dosage A but then decreased to

treatment dosage C. Cobalt (Co) showed an increase

on treatment dosage B but very little change for A

and C. Chlorine (Cl) increased with increased Mn.

Cl reached nearly a 100% increase for treatment

dosage C. Mn impacts electrolyte’s balance.

The observations worthy of discussion are that

Mo showed an increase of over 100% by introducing

Mn at the dosage level A. But then as dosage levels

increase the amount of change for Mo decreases.

This suggests a competition mechanism between Mn

and Mo for retention or accumulation in the kidney.

Very few elements showed decrease in

accumulation due to Mn treatment. This would

suggest that Mn increases accumulation of the

majority of the elements in the kidney. Also similar

to Mo, the lower dosage of group A had the least

amount of decrease in accumulation from control for

all the elements. Then with increased Mn intake, the

elemental accumulation either increases or decreased

more than those obtained with the lower Mn dosage.

This suggests that Mn has a concentration-related

impact on accumulation.

The kidney controls electrolyte balance to collect

or accumulate excessive levels of different elements

that may be present in the body. By introducing Mn

treatment, this also increases the overall elemental

accumulation compared to other organs. Next step

analysis would be a mass balance and how well the

kidney flushes elevated concentrations from the

body.

-1

-0.5

0.5

1.5

2.5

A B C

Mn Treatment Dosage

Figure 2: Results of kidney with Mn treatment for Group

A, B, and C as compared with control.

3.3 Lung

For the lung, Hg also shows significant increase

from control. Treatment dosage B showed the

highest Hg levels but dosage C induced almost a

300% increase. Many elements showed at or above

50% increase for the highest Mn dosage with all of

them becoming increasingly concentrated with

increased Mn dosage. Mn treatment shows evidence

that there is a wide range of elements that have

concentration impacts related to Mn.

Mn ingested by diet has a very large impact on

elemental accumulation of the lungs. This

relationship is extremely important because one of

ICFEPP 2019 - International conference on Future Environment Pollution and Prevention

the most common methods of exposure and intake is

by the lungs and breathing air. From this data set, a

link to practical use is that an increased Mn intake

may allow the subject to be at higher risk for toxic

elemental accumulation in the lungs that could lead

to illness and other health concerns.

This data shows effect via ingestion then through

the blood to the lungs which is different than most

studies that look at inhalation and the accumulation

by inhalation. What is shown by this analysis is that

orally ingested Mn can increase the accumulation of

elements ingested orally. For further investigation,

the relationship between orally ingested Mn and the

accumulation of elemental exposure by inhalation

would be important. Miners and similar type of

industrial workers are often exposed to highly

elevated inhalation of different elements. This link

between orally ingested Mn and elemental exposure

by inhalation could greatly impact mining personnel

protective equipment and medical treatment of

miners. Current exposure limits are debatable and

may need to be adjusted with consideration of

possible Mn ingestion.

Figure 3: Results of lung with Mn treatment for Group A,

B, and C as compared with control.

3.4 Spleen

Mn shows increased concentration compared to

control for increased Mn dosages indicating a

possible correlation. V has drastic variations going

from nearly 75% less than control to nearly 3 times

the control value. Co shows an increased

concentration for only one dosage but almost no

change for the other dosage treatments. Iron (Fe)

shows elevated concentration for dosage A and then

decreases to negative values for the largest Mn

dosage.

The fractional change from control is very

sporadic with the spleen. At one dosage level a

particular element will show an increase and then at

a different dosage show a decrease. Cr is one

element that at the small Mn dosage shows a large

increase but with increased Mn the fractional change

of Cr goes negative. At a low dosage more Cr is

accumulated and at a high dosage less Cr is

accumulated. This suggests that starting with low

Mn treatment creates a mechanism allowing more Cr

to accumulate. Then as Mn increases it competes

with and displaces Cr to levels even below the

control.

In the case of Cu, treatment with Mn reduces

accumulation. The reduced accumulation is

relatively the same at all three Mn concentrations.

This suggests that Cu has an interaction with Mn but

is not correlated to Mn dosage concentration.

-1

-0.5

0.5

1.5

2.5

A B C

Mn Treatment Dosage

Figure 4: Results of spleen with Mn treatment for Group

A, B, and C as compared with control.

3.5 Liver

The liver is not showing any individual elements

that have drastic increases as compared to organs

discussed in previous sections. Of all the elements

there are only five that show greater than a 50%

change and only one element that shows over a

100% change. Cr shows an increasing trend that

relates to increased Mn dosage. Decreases in

Rubidium (Rb) and Iodine (I) were not observed in

previous organs as with the liver.

In comparison to the spleen, Cr in the liver

increases with increased Mn as opposed to the

spleen where Cr was observed to decrease with

increased Mn. This observation may suggest a

relationship between increasing accumulation in the

liver and decreasing accumulation in the spleen. An

observation that has not been seen on previous

organs is with I. Iodine starts out with negative

accumulation at the lower Mn dosage. As Mn

dosage increases, Iodine fractional change becomes

Dietary Intakes Inﬂuence on Metallomic Distribution in Vital Organs and Their Implications

less. This suggests a mechanism that has the most

impact at lower dosage and then has less impact as

Mn dosages increase.

Another observation is that as Mn dosage

increases, more elements trend to a negative

accumulation. For unwanted or toxic elements, an

increased Mn dosage treatment reduces the

accumulation in the liver. As discussed with results

obtained with the kidney, the liver serves a similar

function in detoxification. This data supports that

increased Mn treatment provides for less

accumulation in the liver. There could be at least

two possible mechanisms. First is that increased Mn

treatment increases accumulation in other organs so

that the element is not available to accumulate in the

liver. A second possibility is that Mn treatment

improves the liver’s ability to filter out or flush away

unwanted elements.

-1

-0.5

0.5

1.5

A B C

Mn Treatment Dosage

Figure 5: Results of liver with Mn treatment for Group A,

B, and C as compared with control.

3.6 Pituitary

The pituitary shows an interesting trend that for each

treatment, the amount of change from control is

relatively the same. The same elements that show

increases show nearly the same increase for each

dosage treatment. Then for the elements that show a

decrease, maintain similar decreases cross the

dosage treatments.

In the pituitary, Mn treatment has a baseline

impact that is unrelated to Mn dosage level. The

presence of Mn has an impact but the concentration

of Mn dosage has little impact. . As overall more

elements have a negative impact for dosage

treatments in groups B and C compared to A. The

pituitary is not significantly impacted by Mn

treatment compared to other organs likely due to the

effect of the blood brain barrier.

-1

-0.5

0.5

1.5

A B C

Mn Treatment Dosage

Figure 6: Results of pituitary with Mn treatment for Group

A, B, and C as compared with control.

3.6 Uterus

The uterus shows more concentration decreases than

increases. Co, Cr and Cu show the most significant

increases. V, Fe and F show the most significant

decreases. For most elements, Mn decreases

accumulation. The large increases in heavy metals

(e.g. Co, Cr, and Cu) should be a signal for more

detailed investigation. The uterus is the key organ in

reproduction and significant accumulations can have

a detrimental impact on birth defects and maternally

associated diseases. As an overall observation,

increased Mn may be used to reduce elemental

accumulation in the uterus as well.

-1

-0.5

0.5

1.5

A B C

Mn Treatment Dosage

Figure 7: Results of Uterus with Mn treatment for Group

A, B, and C as compared with control.

4 DISCUSSIONS

Each organ has different characteristics as indicated

by some showing overall accumulating

concentrations and some showing overall

ICFEPP 2019 - International conference on Future Environment Pollution and Prevention

diminishing concentrations, and others showing

mixed trends with increasing elemental

concentrations and decreasing elemental

concentrations. In a few instances, there were some

elements that showed a possible correlation with Mn

dosage. Both increasing concentrations with

increased Mn dosage and decreasing with increasing

Mn dosage were present suggesting positive and

negative correlations.

Three main observations can be concluded from

this analysis:

4.1 Elements Showing Increases

In most cases, treatment with Mn showed increased

elemental accumulation. Elements showing

accumulation in at least four organs are: Ca, Mg, Co,

Cr, Cu, Mo, and Se. In this group of elements, there

are some elements with known impacts on human

health and degenerative diseases (e.g., Cu related to

Alzheimer’s and Parkinson’s diseases). The

findings emphasize the importance of more

extensive studies where Mn may have been used in

applications that may have increased human

ingestion such as treatment of drinking water.

Elements showing accumulation in two or fewer

organs are: F, K, Na, Br, Hg, I, Rb, V, and Zn. Even

though accumulation was shown for this group of

elements, only certain organs displayed

accumulation. This is important to help identify

elements that may have more complicated

homeostatic mechanisms and are more selective to

individual organs. In this group, there also are

elements with known health impacts.

4.2 Elements Showing Increases

The liver and uterus show more overall decreased

elemental concentrations. The spleen and pituitary

also had several elements that decreased in

elemental concentration with Mn treatment.

Elements that show decreasing concentrations in

three or more organs are: Br, Hg, Se, V, and Zn.

Elements that show decreased concentration in one

organ are: Cl, Fe, K, Mg, Na, Al, Cr, Fe, I, and Rb.

Overall, more elements showed increased

concentrations or accumulation due to Mn treatment

than elements that showed decreased concentrations.

4.3 Overall Accumulating,

Diminishing, and Mixed

The organs that showed decreasing elemental

concentrations were the liver and uterus. The uterus,

showing a decrease in overall concentration, may

provide a link to the impact of Mn exposure and

possible birth defects. The liver, showing decreased

concentrations, may have two possible impacts.

First is the possibility that the elements are being

excreted from the body. This may be a positive

impact in regard to applications that would need to

reduce the concentration of a particular toxin in the

body. The second possible result in the liver

showing reduced elemental concentrations is that the

function of the liver is being reduced and therefore is

not pulling contaminants from the body.

5 CONCLUSIONS

From the literature search listed in this study, it is

evident there are many focused and detailed studies

showing the health impacts due to increased

elemental concentrations of particular elements.

One study identified Cu, Zn, Fe, and Mn are

essential for normal brain function, but also show

that above normal concentrations may lead to no

detectable (ND) symptoms. In this study, we found

the concentration of Cu is increasing in many organs

due to Mn treatments. In an evaluation of all brain

data, Cu decreases by 100% from adult control (AC)

to old control (OC) rats (Wright et al.).

The treatment of Mn could be beneficial in some

cases and detrimental in other cases. An increase in

Cu concentration (≈ 10%) in the brain may be

beneficial but an increase in Hg in the heart (≈

1500%) may be detrimental to humans. This data

set will provide a key piece in understanding human

health effects due to elevated elemental (i.e., heavy

metal) ingestion over the full life span.

The fact that there is hardly any information

available regarding elemental accumulation in

organs such as spleen, pituitary, and uterus makes

this massive collective study ever more valuable.

ACKNOWLEDGEMENTS

We want to acknowledge that Dr. Thomas K.C.

Leung, Institute of Molecular and Cell Biology,

Proteos, Singapore for his contributions in collecting

and organizing the data, and Professor Margret

Minsky, University of London for organizing and

conducting the elemental analyses.

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ICFEPP 2019 - International conference on Future Environment Pollution and Prevention