Mercury Toxicity
Mercury is a liquid metal at ordinary temperatures and pressures. More importantly, it is a reactive element. Since it was first isolated, mankind has developed an increasingly vast array of uses for mercury. The advances in mercury toxicology have turned full circle, the knowledge of mercury poisoning comes from studies of cases of acute poisoning. The present danger presents itself as a chronic, low-level chronic exposure, also known as mercurialism and micromercurialism.
Most people are familiar with elemental mercury in liquid state found in a thermometer or thermostat. The most common source of chronic exposure is from Amalgam in dental fillings, amalgam has been used for mettallurgical purposes releasing mercury vapor. Vaccinations contain thimerosal used as a preservative, exposing undeveloped organs at a critical stage. Then bioaccumulation of methyl mercury in seafood, industrial uses and coal fired power plants.
Monomethylmercury (MeHg) participates directly in biochemical reactions. MeHg is crated both by humans and by the environment. Industry uses MeHg, and in the past poisoning were due to industrial discharge. MeHg is also created through biomethylation processes in the environment and bioaccumulates primarily in fish and people who eat fish.
Mercury compounds vapor can enter the body through various pathways, including inhalation of vapor, ingestion, and skin contact. Most of the exposure to elemental mercury comes from inhalation of mercury vapor, injections of thimerosal and ingestion of MeHg.
Mercury vapor is nonpolar, monatomic gas, and lipid-soluble. For example, let's follow the path of inhaled mercury vapor. From the lungs it dissolves in blood plasma, and from there it has access to diffuse into the cell in the body. Once inside a cell, mercury dissolves in blood plasma, and from there it has access to diffuse into any cell in the body. Once inside a cell, mercury vapor, itself unreactive is oxidized to the highly toxic mercury (+2) ion. This is also known a divalent mercury. This oxidation process is mediated by the enzyme catalase. Catalase normally functions in a two-step process to remove hydrogen peroxide from cells. However, in the second step of this process, mercury vapor can be oxidized to divalent mercury.
There is also oxidized to divalent mercury, this divalent mercury in the brain leads to strange symptoms, including erethism. Mercury is also found to be the process linking behavioral symptoms and Alzheimer's.
Monomethylmercury (MeHg) is estimated 100 to 1000 times more toxic than elemental mercury in humans. MeHg seems to specifically target the Central Nervous System (CNS). Until recently, this was a mystery, as the CNS enjoys the protection of the Blood Brain Barrier (BBB). The BBB consists of tightly packed endothelial cells that line the walls of the blood capillaries in the CNS.
The key to understanding why MeHg is so toxic is to see that structural similarities in biochemical reactions can lead to active transport of toxins. In the case of organisms with a highly advanced CNS, this active transport can lead to accumulation of MeHg in the brain. The pathway of MeHg from the bloodstream to the brain is complicated, to understand the pathway a number of processes are involved:
- MeHg in blood plasma can combine with cysteine, forming a compound that is structurally similar to the amino acid methionine.
- This MeHg-cysteine compound is actively transported into the endothelial cells in the BBB, on the methionine carrier.
- A high level of reduced glutathione is maintained in the endothelial cells, and the MeHg switches from a cystein carrier to a glutathione carrier.
- MeHg-glutathione is actively transported out of the endothelial cells and into the brain.
- In the brain, the hydrolysis of MeHg-glutathione generates MeHg-cysteine.
This MeHg-cysteine can now enter nerve cells in the brain, where it accumulates. The reason why it accumulates is unknown, but it is known that reduced glutathione levels are low in some neurons. It is thought that this low level of reduced glutathione might allow MeHg-cysteine to remain in the cells, unlike in the endothelial cells.
Furthermore, since MeHg-cysteine is structurally similar to the amino acid methionine, it may interfere with protein synthesis in nerve cells. This is especially likely, since methionine is always the first amino acid involved with protein synthesis. However, the exact process is not yet fully understood.
The toxicity of MeHg in the developing brain is even more complicated. MeHg has been shown to affect proteins that are involved in the assembly of microtubules in the nerve cells cytoskeleton. By noting that microtubules are essential for nerve cell division and migration, we see how MeHg can affect brain growth and development. This is why the fetal brain is particularly sensitive to MeHg. Also, the BBB of the fetal brain is about three times more active in amino acid transport, which only makes the MeHg brain concentration rate higher.
MeHg also produces subtle changes in the production and secretion of neurotransmitters in the developing brain, which alters brain development in subtle ways. For example, MeHg has been shown to accumulate in astrocyte cells in the developing brain. One role of astrocytes is to regulate levels of the amino acid glutamate in the developing brain. It happens that glutamate is toxic to the developing brain. Since an inhibition of astrocyte cell function will enhance glutamate levels, we can see an indirect path for mercury poisoning in the brain. This is a very complex subject, and very little is known about the exact developmental changes that are expected from MeHg.
The standard methods for determining the concentration of mercury compounds in the body involve urine, blood, fecal and hair samples with a challenge test using a small portion of chelator to push out mercury. The problem with these methods is that they only show a recent history of mercury exposure, whereas mercury is a cumulative toxin. Since these tests cannot account for past exposures, they are only valid indicators of recent, acute exposure. This is part of the reason that there is so little known about chronic, low-level mercury exposure.
Unfortunately, by the time symptoms appear, usually the damage is already done. This is complicated by the fact that mercury toxicity is difficult to diagnose. However, when mercury contamination is diagosed and there is still a concentration of mercury in the body. Removal of all sources is first necessary, followed by chelation therapy that may help. Chelation therapy involves the formation of a complex of mercury with a chelate ligand. DMSA, EDTA and DMPS are such chelating ligands used in the treatment of heavy metals. Do not use a chelator without fully understanding which metals they chelate and the possibility of permanent damage due to the organs lack of ability to remove toxins. Doses of chelating agents increase the blood and urine concentrations of mercury, and thus help eliminate it from the body.
Mercury molecule and mercury molecule bound as in chelation.
Most of the effects involve complex biochemical reactions that are affected by the presence of mercury compounds. These include the immune system, particular organs, brain growth and development and behavioral patterns. Chronic mercury exposure is an important area of study.
- Amalgam Amalgam a substance formed by the affinity of elemental mercury to other metals. Common amalgams of mercury involve gold or silver. Gold amalgams are utilized in the mining industry, and silver amalgams are utilized in dentistry as fillings.
- Biomethylation This is a process where organisms in the environment methylate elemental mercury. This is believed to be a protective measure, as the methylated mercury is then released from the organism. However, MeHg bioaccumulates in fish, and is also toxic to organisms with an advanced central nervous system.
- Catalase Catalase is an enzyme that occurs in cells. It functions to remove dangerous hydrogen peroxide from cells.
- Chelation The formation of a coordination compound with a chelate (claw-like) ligand. These complexes are generally quite stable.
- Endothelial cells Endothelial cells form a tight packing around the capillaries in the brain, effectively forming the Blood Brain Barrier. These cells are highly active in amino acid transport, especially in the fetal brain.
- Erethism The name given to a group of bizarre behavioral symptoms. Erethism is sometimes a sign of mercury poisoning. Symptoms are similar to the behavior of the Mad Hatter in Alice in Wonderland.
- Glutathione Glutathione is a chemical present in cells to maintain a reducing atmosphere as protection against oxygen radicals.
- Ligand Ligands are molecules or atoms bound to a central metal ion or atom by coordination of its lone electron pairs.
- Neurotransmitter These are the chemical messengers for neurons. They participate in complex interactions in the central nervous system, both during normal function, and during growth and development.
- Transmutation The process where one element can be changed into another element. This was a favorite topic in early alchemy, especially when heavy metals and gold were involved.