International Journal of
Environmental Research
and Public Health
Review
Mercury Exposure and Heart Diseases
Giuseppe Genchi
1
, Maria Stefania Sinicropi
1,
*, Alessia Carocci
2,
*, Graziantonio Lauria
1
and Alessia Catalano
2
1
Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria,
87036 Arcavacata di Rende (Cosenza), Italy; giuseppe.genchi@unical.it (G.G.); glauria@unical.it (G.L.)
2
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “A. Moro”, 70125 Bari, Italy;
alessia.catalano@uniba.it
* Correspondence: s.sinicropi@unical.it (M.S.S.); alessia.carocci@uniba.it (A.C.);
Tel.: +39-098-449-3200 (M.S.S.); +39-080-544-2745 (A.C.)
Academic Editors: Timothy Dvonch and Nicola Pirrone
Received: 9 October 2016; Accepted: 30 December 2016; Published: 12 January 2017
Abstract:
Environmental contamination has exposed humans to various metal agents, including
mercury. It has been determined that mercury is not only harmful to the health of vulnerable
populations such as pregnant women and children, but is also toxic to ordinary adults in various ways.
For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure
to this metal from both natural and artificial sources is significantly increasing. Recent studies
suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular,
reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and
carcinogenicity. Possible biological effects of mercury, including the relationship between mercury
toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease,
and myocardial infarction, are being studied. As heart rhythm and function are under autonomic
nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also
impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac
parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate
variability, particularly early exposures in children. The mechanism by which mercury produces toxic
effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve
an increase in oxidative stress. The exposure to mercury increases the production of free radicals,
potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of
antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the
toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.
Keywords: mercury; antioxidants; cardiovascular diseases; cardiotoxicity; chelating agents
1. Introduction
As far back as 20,000–30,000 years BC, Paleolithic artists used various pigments, including
cinnabar (mercuric sulfide, HgS) due to its red color, to draw hunting scenes with bison, bulls, stags,
horses, humans, and handprints in negative images on cave walls (Altamira-Spain and Lascaux-France
caves). Even the Chinese and the Romans (VII–VI century BC) employed cinnabar for pictorial
art. Subsequently, mercury has been used in thermometers, sphygmomanometers, barometers,
incandescent lights, and batteries; moreover, it was employed in dental amalgams (typically composed
of 50% mercury, 25% silver, and 25% tin, copper, and nickel) [
1
], germicidal soaps, and skin creams [
2
].
Mercury has also been used to purify gold and silver minerals by forming amalgams in mines in the
Brazil basin, in Laos, and in Venezuela. For a long time many medicines, cosmetics, and vaccines
contained small amounts of organic mercury compounds, like ethylmercury thiosalicylate (thimerosal),
as preservatives. Medicinal uses of mercury have included its use as a diuretic, antiseptic, skin
Int. J. Environ. Res. Public Health 2017, 14, 74; doi:10.3390/ijerph14010074 www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2017, 14, 74 2 of 13
ointment, laxative, and as a treatment of syphilis. Mercury has also been used as a poison. The great
sculptor Benvenuto Cellini, when poisoned by a sublethal dose of mercury, was apparently cured of
a severe case of syphilis [
3
]. History has left us a lot of information on the effect of mercury toxicity.
The earliest recorded death by mercury is the Chinese Emperor Qin Shi Huang (260–210 BC). According
to legend, the cause of death most likely was mercury poisoning, due to his immortality treatments [
4
].
Certainly, the exposure to mercury brought harmful effects to health of humans and called the attention
of the scientific world after the epidemics occurred in Japan and in Iraq. In Japan, two methylmercury
poisoning events are worthy of mention. These accidents, resulting from the deposition of industrial
waste containing large quantities of methylmercury [
5
,
6
], occurred in the Japanese village of Minamata
Bay (1953) and along the Agano river in Niigata (1964). Mercury, bioaccumulated within the food chain
from plankton, microorganisms up to shellfish and fish, was then ingested, thus the inhabitants of
Minamata Bay began to exhibit symptoms of neurological illness, such as uncontrollable trembling, loss
of motor control, speech impairment, sensory disturbance, blindness, mental retardation, coma, and
death. Infants, whose mothers were infected, developed mental retardation, peripheral neuropathy,
and cerebral palsy. Additionally, in 1971 in rural Iraq, severe methylmercury intoxication occurred
when bread was prepared and eaten from wheat seeds that had been treated with fungicides containing
organic mercury compounds [
6
,
7
]. The incidents in Japan and Iraq produced not only deaths, but also
multiple and long-lasting intoxication symptoms, including blindness, deafness, mental retardation,
cerebral palsy, and dysarthria especially in children exposed in utero [8].
Methylmercury, the most toxic mercury compound, is an organic mercurial compound primarily
found as a pollutant in rivers, lakes, and oceans. Methylmercury is usually formed naturally through
biomethylation of mercury, carried out by aquatic anaerobic sulfate-reducing bacteria [
9
,
10
] (Figure 1).
It also derives from anthropogenic sources, and when formed will be released into rivers, lakes, and
oceans. Consequently, people whose diet consists mainly of shellfish and fish may be exposed to
high levels of methylmercury [
11
]. Approximately 85% of methylmercury ingested is absorbed in the
gastrointestinal tract, while about 5% is present in blood and 10% in the brain. In many developing
countries, mercury is still a major problem which requires actions for proper control. Many efforts
should be placed on the removal of anthropogenic sources of mercury and the prevention of exposure.
Int. J. Environ. Res. Public Health 2017, 14, 0074 2 of 13
thiosalicylate (thimerosal), as preservatives. Medicinal uses of mercury have included its use as a
diuretic, antiseptic, skin ointment, laxative, and as a treatment of syphilis. Mercury has also been
used as a poison. The great sculptor Benvenuto Cellini, when poisoned by a sublethal dose of
mercury, was apparently cured of a severe case of syphilis [3]. History has left us a lot of information
on the effect of mercury toxicity. The earliest recorded death by mercury is the Chinese Emperor Qin
Shi Huang (260–210 BC). According to legend, the cause of death most likely was mercury poisoning,
due to his immortality treatments [4]. Certainly, the exposure to mercury brought harmful effects to
health of humans and called the attention of the scientific world after the epidemics occurred in Japan
and in Iraq. In Japan, two methylmercury poisoning events are worthy of mention. These accidents,
resulting from the deposition of industrial waste containing large quantities of methylmercury [5,6],
occurred in the Japanese village of Minamata Bay (1953) and along the Agano river in Niigata (1964).
Mercury, bioaccumulated within the food chain from plankton, microorganisms up to shellfish and
fish, was then ingested, thus the inhabitants of Minamata Bay began to exhibit symptoms of
neurological illness, such as uncontrollable trembling, loss of motor control, speech impairment,
sensory disturbance, blindness, mental retardation, coma, and death. Infants, whose mothers were
infected, developed mental retardation, peripheral neuropathy, and cerebral palsy. Additionally,
in 1971 in rural Iraq, severe methylmercury intoxication occurred when bread was prepared and
eaten from wheat seeds that had been treated with fungicides containing organic mercury
compounds [6,7]. The incidents in Japan and Iraq produced not only deaths, but also multiple and
long-lasting intoxication symptoms, including blindness, deafness, mental retardation, cerebral
palsy, and dysarthria especially in children exposed in utero [8].
Methylmercury, the most toxic mercury compound, is an organic mercurial compound primarily
found as a pollutant in rivers, lakes, and oceans. Methylmercury is usually formed naturally through
biomethylation of mercury, carried out by aquatic anaerobic sulfate-reducing bacteria [9,10] (Figure
1). It also derives from anthropogenic sources, and when formed will be released into rivers, lakes,
and oceans. Consequently, people whose diet consists mainly of shellfish and fish may be exposed to
high levels of methylmercury [11]. Approximately 85% of methylmercury ingested is absorbed in the
gastrointestinal tract, while about 5% is present in blood and 10% in the brain. In many developing
countries, mercury is still a major problem which requires actions for proper control. Many efforts
should be placed on the removal of anthropogenic sources of mercury and the prevention of
exposure.
Figure 1. Bioavailabilty and toxic effects of mercury and its compounds. A: Oxidation in air, and
enzymatically in red blood cells and tissues; B: Biomethylation by sulfate-reducing bacteria.
Several studies regarding mercury-related health problems have been carried out in populations
mostly exposed through the consumption of mercury-contaminated fish and other seafood [12]. For
Figure 1.
Bioavailabilty and toxic effects of mercury and its compounds. A: Oxidation in air, and
enzymatically in red blood cells and tissues; B: Biomethylation by sulfate-reducing bacteria.
Several studies regarding mercury-related health problems have been carried out in populations
mostly exposed through the consumption of mercury-contaminated fish and other seafood [
12
].
For decades, the toxic effects of mercury were associated mainly with the central nervous system.
Int. J. Environ. Res. Public Health 2017, 14, 74 3 of 13
However, a growing body of evidence suggests that methylmercury exposure can also lead to
increased risks of adverse cardiovascular impacts in exposed populations. In January 2010, the US
eicosapentaenoic acid (EPA) assembled experts spanning epidemiology, toxicology, clinical medicine,
risk, and exposure assessment to participate in a workshop in Washington DC to review the current
science and literature concerning cardiovascular impacts of MeHg exposure. They studied MeHg
exposure via fish, shellfish, and sea mammal consumption to elicit recommendations about whether
these effects should be included in Hg regulatory impact analyses. The results of this workshop were
reviewed by Roman et al. [
13
]. The authors assessed the causal relationship between MeHg exposure
and an increased risk of cardiovascular health effects by evaluating the plausibility of biological
mechanisms for the cardiovascular toxicity of MeHg and weighing the strength of the human, animal,
and
in vitro
studies linking MeHg with cardiovascular health impacts. In this review, we attempt to
present an understanding of the role that exposure to mercury plays in cardiovascular diseases.
2. Materials and Methods
The review was performed following the principles of the PRISMA statement [
14
]. A literature
search of publications included in the electronic databases was conducted using MEDLINE (via
PubMed) and Google Scholar. The search criteria considered the occurrence of the combination of
the following keywords: mercury toxicity, heart disease, and cardiovascular disease either in the title,
abstracts, or in the text. All the publications found were screened based upon consideration of the title
and abstract in order to assess the relevance of the subject and eligibility. Each author independently
extracted data from each paper regarding the role that exposure to mercury plays in cardiovascular
diseases and discussed the data with the other authors. Then a draft of the manuscript was circulated
to the authors and subsequently revised several times. A final version of the manuscript was then
prepared and finally approved by all the authors.
3. Chemical Forms and Toxicity of Mercury
Mercury (Hg, hydrargyrium from the Latin “liquid silver”) is a heavy metal (atomic number 80;
atomic weight 200.59; density 13.59 g/cm
3
; melting point
−
39
◦
C; boiling point 359
◦
C) with a toxicity
as well-known (World Health Organization 2007) [
15
] as lead and cadmium [
16
,
17
]. Mercury is a
non-transition metal and is an extremely rare element in the Earth’s crust, usually in the form of the
mineral cinnabar (mercury sulfide, HgS), having an average mass abundance of only 0.09 mg/Kg [
18
].
Mercury has three valence states and exists in several forms: inorganic mercury, which includes liquid
metallic mercury and mercury vapor (Hg
0
), mercurous (Hg
+
) and mercuric (Hg
++
) salts, and organic
mercury, with methylmercury (CH
3
Hg, MeHg), ethylmercury (C
2
H
5
Hg, EtHg), and phenylmercury
(C
6
H
5
Hg, PhHg). The biological behavior and clinical significance of the various forms of mercury
vary according to its chemical structure [
19
]. Elemental mercury (Hg
0
), at room temperature, exists
in its liquid form which quickly turns to vapor when heated above room temperature. The high
volatility of Hg
0
prolongs the effects of anthropogenic release and Hg
0
can remain suspended in the
atmosphere for up to one year, where it can be transported and deposited globally. In the atmosphere,
Hg
0
constitutes the majority of mercury (>90%) and is the predominant form in the gaseous phase,
which facilitates the long-range transport of mercury at a global scale [
20
]. Mercury is released into the
environment from both natural and anthropogenic sources. Annually, volcanic (for example Etna and
Stromboli, Sicily, Italy), geothermal outgassing activities (for example the Phlegrean Fields, Pozzuoli,
Italy), thermal springs, earthquakes, erosion, and the volatilization of mercury present in the marine
environment (Agency for Toxic Substances and Disease Registry, ATSDR 1999) [
21
–
23
] release an
estimated 1500 t of mercury to the environment [
24
]. Anthropogenic release occurs from manifold
industrial point sources, chlor-alkali plants [
25
] and coal-fired power plants [
26
] and is estimated to
constitute 2320 t of mercury emitted annually into the atmosphere [
24
]. Hg
0
is oxidized in air to its
inorganic forms (Hg
+
and Hg
++
) and is released during rain events to be deposited in soil and into
the waters of rivers, lakes, and oceans. In its vapor form, metallic mercury is commonly absorbed
Int. J. Environ. Res. Public Health 2017, 14, 74 4 of 13
through the respiratory tract, where it is poorly absorbed in the gastrointestinal tract. Because of its
soluble characteristics, elemental mercury is highly diffusible through cell membranes as well as the
blood-brain and placental barriers to reach target organs. Once in the blood stream, Hg
0
is easily
oxidized in red blood cells and tissues into inorganic Hg
+
and Hg
++
in the presence of catalase and
peroxidase. The inorganic forms, Hg
+
and Hg
++
, have low lipophilicity and thus a limited ability
to cross cell membranes. The mercuric form (Hg
++
) in the bloodstream binds to cysteine sulfhydryl
groups (-SH) on erythrocytes, glutathione, and metallothioneines or is transported suspended in
plasma [
27
]. It is mainly absorbed through the respiratory tract, and in small extent through the skin
(5%–8%) and gastrointestinal tract (3%–5%) (Figure 1). The main excretory pathways include urine
and feces, with a half-life of about two months. In aquatic and soil environments, mercury is primarily
present in its mercuric form, including inorganic (e.g., mercuric hydroxide) and organic mercuric
compounds, and secondarily as Hg
0
[
28
,
29
]. Mercuric compounds can be found in different states,
as mercuric chloride (HgCl
2
, highly toxic and corrosive), mercuric sulfide (HgS, used as a pigment in
paints), and mercury fulminate (Hg(CNO)
2
), used as an explosive detonator). Mercuric mercury in the
blood stream binds to –SH groups on erythrocytes, glutathione, and metallothioneines or is transported
suspended in plasma. There is experimental evidence that this compound is accumulated in the brain
through its binding to cysteines [
30
]. Inorganic mercury, which is derived from industrial release,
is biomethylated to methylmercury (MeHg), primarily by sulfate-reducing bacteria [
9
,
10
,
31
], Although
only a minor fraction of total mercury is present as MeHg (typically less than 10% and 3% in water and
soil/sediment, respectively), the formation of this compound is an important step in mercury cycling.
MeHg is easily absorbed overall into the gastrointestinal tract (Figure 1) and is excreted in feces, and
to a lesser extent in urine. Organic mercury crosses the blood-brain and placental barriers and can
be transmitted to fetus and, through breast milk, babies can assimilate these toxic compounds with
resulting bioaccumulation especially by the liver, brain, kidney, and muscles [
9
]. MeHg bioaccumulate
in the food chain from small creatures to larger predatory fish (i.e., swordfish, shark, king mackerel,
tilefish) and sea mammals and can reach high concentrations in organisms, in particular in aquatic
environments [
28
]. Large predatory fish and sea mammals can contain methylmercury amounts that
are as much as 100,000 times higher than the surrounding water medium. Consequently, populations
with high dietary intake of seafood are likely to be subjected to exposure to high levels of mercury
that has been reported to harm the brain, lungs, kidneys, the nervous and immune systems, and also
the heart and cardiovascular system [
32
]. Nevertheless, seafood and fish represent an important and
great source of proteins, especially for those populations living near seas, lakes, and rivers. Indeed,
fish and shellfish contain proteins, as well as long-chain omega-3 polyunsaturated fatty acids (PUFA),
including EPA and docosahexaenoic acid (DHA) (Figure 2), and trace elements as selenium, calcium,
and magnesium [
33
]. The presence of mercury was detected in a wide variety of foods including dairy
products as pasta, eggs, meats, poultry, and vegetables. However, the level of mercury in these foods
is very low compared to the level found in fish.
Int. J. Environ. Res. Public Health 2017, 14, 0074 4 of 13
gastrointestinal tract. Because of its soluble characteristics, elemental mercury is highly diffusible
through cell membranes as well as the blood-brain and placental barriers to reach target organs. Once
in the blood stream, Hg
0
is easily oxidized in red blood cells and tissues into inorganic Hg
+
and Hg
++
in the presence of catalase and peroxidase. The inorganic forms, Hg
+
and Hg
++
, have low lipophilicity
and thus a limited ability to cross cell membranes. The mercuric form (Hg
++
) in the bloodstream binds
to cysteine sulfhydryl groups (-SH) on erythrocytes, glutathione, and metallothioneines or is
transported suspended in plasma [27]
. It is mainly absorbed through the respiratory tract, and in
small extent through the skin (5%–8%) and gastrointestinal tract (3%–5%) (Figure 1). The main
excretory pathways include urine and feces, with a half-life of about two months. In aquatic and soil
environments, mercury is primarily present in its mercuric form, including inorganic (e.g., mercuric
hydroxide) and organic mercuric compounds, and secondarily as Hg
0
[28,29]. Mercuric compounds
can be found in different states, as mercuric chloride (HgCl
2, highly toxic and corrosive), mercuric
sulfide (HgS, used as a pigment in paints), and mercury fulminate (Hg(CNO)
2), used as an explosive
detonator). Mercuric mercury in the blood stream binds to –SH groups on erythrocytes, glutathione,
and metallothioneines or is transported suspended in plasma. There is experimental evidence that
this compound is accumulated in the brain through its binding to cysteines [30]. Inorganic mercury,
which is derived from industrial release, is biomethylated to methylmercury (MeHg), primarily by
sulfate-reducing bacteria [9,10,31], Although only a minor fraction of total mercury is present as
MeHg (typically less than 10% and 3% in water and soil/sediment, respectively), the formation of this
compound is an important step in mercury cycling. MeHg is easily absorbed overall into the
gastrointestinal tract (Figure 1) and is excreted in feces, and to a lesser extent in urine. Organic
mercury crosses the blood-brain and placental barriers and can be transmitted to fetus and, through
breast milk, babies can assimilate these toxic compounds with resulting bioaccumulation especially
by the liver, brain, kidney, and muscles [9]. MeHg bioaccumulate in the food chain from small
creatures to larger predatory fish (i.e., swordfish, shark, king mackerel, tilefish) and sea mammals
and can reach high concentrations in organisms, in particular in aquatic environments [28]. Large
predatory fish and sea mammals can contain methylmercury amounts that are as much as
100,000 times higher than the surrounding water medium. Consequently, populations with high
dietary intake of seafood are likely to be subjected to exposure to high levels of mercury that has been
reported to harm the brain, lungs, kidneys, the nervous and immune systems, and also the heart and
cardiovascular system [32]. Nevertheless, seafood and fish represent an important and great source
of proteins, especially for those populations living near seas, lakes, and rivers. Indeed, fish and
shellfish contain proteins, as well as long-chain omega-3 polyunsaturated fatty acids (PUFA),
including EPA and docosahexaenoic acid (DHA) (Figure 2), and trace elements as selenium, calcium,
and magnesium [33]. The presence of mercury was detected in a wide variety of foods including
dairy products as pasta, eggs, meats, poultry, and vegetables. However, the level of mercury in these
foods is very low compared to the level found in fish.
Figure 2. Main fatty acids of the omega-3 polyunsaturated fatty acids (PUFA) group.
Methylmercury may also result from methylation of inorganic mercury by microorganisms in
the mouth, when mercury vapor is released from amalgam dental fillings [34], and from
Figure 2. Main fatty acids of the omega-3 polyunsaturated fatty acids (PUFA) group.
Int. J. Environ. Res. Public Health 2017, 14, 74 5 of 13
Methylmercury may also result from methylation of inorganic mercury by microorganisms in the
mouth, when mercury vapor is released from amalgam dental fillings [
34
], and from non-enzymatic
methylation, when Vit B12 in the form of methylcobalamin donates a methyl group to mercury [
35
].
The different mercury forms are interconvertible
in vivo
; for example, inhaled elemental mercury
vapor is absorbed through the mucous membrane of the lungs and is rapidly oxidized to other forms.
The organic compounds of mercury have a higher solubility in lipids than the inorganic species, thus
they diffuse more easily through the lipid bilayer of biological membranes, increasing their potential
toxicity. Mercury absorbed in the body mainly accumulates in the kidneys and brain. The half-life of
mercury in the body is about 70 days.
Mercury has no known physiological role in human metabolism; furthermore, the human body
lacks effective mechanisms to excrete it [
36
]. Mercury is not actively excreted by the human body;
on average, during the life span of a 70–75 kg human being up to 13 mg of mercury is accumulated
in the human body [
37
]. Mercury is the most dangerous of all heavy metals to which humans and
wildlife can be exposed. Both Hg
0
and MeHg are neurotoxic, whereas inorganic mercury salts are
nephrotoxic [
38
]. Mercury links to numerous biological structures blocking their activity. Indeed, it has
a high affinity for sulfhydryl groups (-SH) of aminoacids, proteins, enzymes, and sulfur-containing
antioxidants such as N-acetylcysteine (NAC),
α
-lipoic acid (ALA), and glutathione (GSH) (Figure 3).
Glutathione provides about 30%–40% of the plasma antioxidant capacity, and is the most potent
intracellular and mitochondrial antioxidant for protecting against oxidative stress, inflammation, and
cardiovascular diseases [36,37,39–42].
Int. J. Environ. Res. Public Health 2017, 14, 0074 5 of 13
non-enzymatic methylation, when Vit B12 in the form of methylcobalamin donates a methyl group
to mercury [35]. The different mercury forms are interconvertible in vivo; for example, inhaled
elemental mercury vapor is absorbed through the mucous membrane of the lungs and is rapidly
oxidized to other forms. The organic compounds of mercury have a higher solubility in lipids than
the inorganic species, thus they diffuse more easily through the lipid bilayer of biological membranes,
increasing their potential toxicity. Mercury absorbed in the body mainly accumulates in the kidneys
and brain. The half-life of mercury in the body is about 70 days.
Mercury has no known physiological role in human metabolism; furthermore, the human body
lacks effective mechanisms to excrete it [36]. Mercury is not actively excreted by the human body;
on average, during the life span of a 70–75 kg human being up to 13 mg of mercury is accumulated
in the human body [37]. Mercury is the most dangerous of all heavy metals to which humans and
wildlife can be exposed. Both Hg
0
and MeHg are neurotoxic, whereas inorganic mercury salts are
nephrotoxic [38]. Mercury links to numerous biological structures blocking their activity. Indeed, it has
a high affinity for sulfhydryl groups (-SH) of aminoacids, proteins, enzymes, and sulfur-containing
antioxidants such as N-acetylcysteine (NAC), α-lipoic acid (ALA), and glutathione (GSH) (Figure 3).
Glutathione provides about 30%–40% of the plasma antioxidant capacity, and is the most potent
intracellular and mitochondrial antioxidant for protecting against oxidative stress, inflammation, and
cardiovascular diseases [36,37,39–42].
Figure 3. Antioxidants such as N-acetylcysteine (NAC), α-lipoic acid (ALA), and glutathione (GSH).
Indeed, mercury induces oxidative stress and mitochondrial dysfunctions. The latter occur at
the NADH (reduced nicotinamide adenine dinucleotide) level: ubiquinone oxidoreductase
(complex I of the respiratory chain), cytochrome C, and cytochrome oxidase (complex IV of the
respiratory chain), by causing displacement of Fe
2+
and Cu
+
, by determining depolarization and
autoxidation of the inner mitochondrial membrane with a reduction in adenosine 5’-triphosphate
(ATP) synthesis, depletion of glutathione, and increased lipid peroxidation [43]. Physiologic
consequences include increased hydrogen peroxide, depletion of mitochondrial glutathione,
increased lipid peroxidation, oxidation of pyridine nucleotides NAD(P)H (nicotinamide adenine
dinucleotide phosphate), and altered calcium homeostasis [43]. Mercury binds to metallothioneines,
replacing zinc, copper, and other trace metals, and competes for selenium, reducing the effectiveness
of the metalloenzymes. In addition, the complex mercury-selenium reduces the availability of
selenium into the formation of the glutathione peroxidase, an enzyme that breaks hydrogen peroxide
and other toxic products. Omega-3 polyunsaturated fatty acids of fish and selenium antagonize some
of the adverse effects of this heavy metal [44–47].
Figure 3. Antioxidants such as N-acetylcysteine (NAC), α-lipoic acid (ALA), and glutathione (GSH).
Indeed, mercury induces oxidative stress and mitochondrial dysfunctions. The latter occur at the
NADH (reduced nicotinamide adenine dinucleotide) level: ubiquinone oxidoreductase (complex I of
the respiratory chain), cytochrome C, and cytochrome oxidase (complex IV of the respiratory chain),
by causing displacement of Fe
2+
and Cu
+
, by determining depolarization and autoxidation of the inner
mitochondrial membrane with a reduction in adenosine 5’-triphosphate (ATP) synthesis, depletion
of glutathione, and increased lipid peroxidation [
43
]. Physiologic consequences include increased
hydrogen peroxide, depletion of mitochondrial glutathione, increased lipid peroxidation, oxidation of
pyridine nucleotides NAD(P)H (nicotinamide adenine dinucleotide phosphate), and altered calcium
homeostasis [
43
]. Mercury binds to metallothioneines, replacing zinc, copper, and other trace metals,
and competes for selenium, reducing the effectiveness of the metalloenzymes. In addition, the complex
mercury-selenium reduces the availability of selenium into the formation of the glutathione peroxidase,
an enzyme that breaks hydrogen peroxide and other toxic products. Omega-3 polyunsaturated fatty
acids of fish and selenium antagonize some of the adverse effects of this heavy metal [44–47].