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TOXIC CAUSES OF PARKINSON'S DISEASE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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TOXIC CAUSES

A small proportion of cases have a toxic cause as the sole or a partial cause of Parkinson's Disease. The toxic exposure usually has to be acute or chronic. Symptoms normally develop when the toxic exposure occurs or soon after, or gradually increase over time when the exposure persists. Symptoms do not develop years later as is sometimes claimed. Avoidance of the source of toxicity can lead, in most cases, to a reduction in the symptoms but with some toxins this can take years.

 

ANNONACEAE

Annonaceae is a family of flowering plants that is also called the custard apple family. Some annonaceae species produce edible fruits. Annonaceae contain acetogenins. In Guadeloupe, Annonaceae are consumed as herbal teas and fruits, especially soursop. Annonacin, which is the most abundant acetogenin, is toxic to dopaminergic neurons in nanomolar concentrations. Acetogenins are potent mitochondrial toxins, like other Parkinsonism inducing compounds. The concentrations of annonacin, the major acetogenin in Annona Muricata, are so high that one fruit or can of nectar per day is more in a year than induced brain lesions in rats receiving purified annonacin by intravenous infusion.

                                                                                                                                                                                   CARBON DISULFIDE

Carbon disulfide is a colourless, flammable, and poisonous liquid with the chemical formula CS2. Carbon disulfide is in pesticides used as fumigants, disulfiram, which is a drug used in the treatment of chronic alcoholism, industrial solvents, and solvents used in the production of viscose rayon and cellophane film. Carbon disulfide interferes with the enzyme pyridoxal 5-phosphate, which is essential for the formation of dopamine from L-dopa. So carbon disulfide might cause Parkinson's Disease symptoms by reducing the formation of L-dopa.

                                                                                                                                                                                                                         CARBON MONOXIDE

Carbon monoxide is a colourless, odourless, and tasteless gas that is slightly less dense than air. Carbon monoxide is produced from the partial oxidation of carbon containing compounds when there is not enough oxygen to produce carbon dioxide. Common sources are motor vehicle exhaust fumes, and cigarette smoke. It also forms when fuels such as coal, paraffin, oil or wood, and especially natural gas, do not burn completely in appliances such as heaters, furnaces, stoves, water heaters, and ovens. However, carbon monoxide rarely causes Parkinson's Disease. It normally requires the person having gone in to a coma as a result of the carbon monoxide poisoning before symptoms of Parkinson's Disease develop.

                                                                                                                                                                                                                     COPPER

Copper, whose chemical symbol is Cu, is a chemical element that is required as an essential nutrient, but which can be toxic in large quantities. Common causes of copper toxicity include Wilson's Disease in which there is a genetic accumulation of copper, copper mines, copper cooking pots, copper plumbing, extreme consumption of nutritional supplements that contain copper. Excessive copper can cause the formation of a copper-dopamine complex, which leads to the oxidation of dopamine to aminochrome.

                                                                                                                                                                                                                      CYANIDE
                                                                                                                                                                                     Cyanide is contained in drugs such as potassium cyanide and sodium cyanide. Cyanides can also be produced by certain bacteria, fungi, and algae, and are found in a number of foods and plants. Cyanide occurs naturally in cassava roots (manioc). Fruits that have a pit, such as cherries or apricots, often contain either cyanides or cyanogenic glycosides in the pit. Bitter almonds, from which almond oil and flavouring is made, also contain cyanide. Hydrogen cyanide is contained in vehicle exhaust and in tobacco smoke. The smoke of burning plastics contains hydrogen cyanide, and so house fires often result in cyanide poisonings. Cyanides are one of the very few soluble compounds of gold and thus are used in electroplating, gold mining, metallurgy and jewellery for chemical gilding, buffing, and extraction of gold. Cyanides and hydrogen cyanide are used in the production of chemicals, photographic development, making plastics, fumigating ships, and some mining processes. Potassium ferrocyanide is used to achieve a blue colour on cast bronze sculptures.

                                                                                                                                                                                                                            CYCAD SEEDS

Cycad seeds of the Cycas micronesica contain ss-methylamino-L-alanine (BMAA), which have been implicated as the cause of toxicity due to the involvement of a product of BMAA and a beta-carbamate. Cycad seeds, by different means, can cause Amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC). This occurs in Guam, which is in the Mariana islands in the Pacific Ocean, the Kii peninsula of Japan, and New Guinea, which is divided between Indonesia and Papua New Guinea.


DIELDRIN
                                                                                                                                                                                     Dieldrin is used as a pesticide. Dieldrin was the most frequently detected Organochlorine pesticide in people with Parkinson's Disease thereby suggesting that dieldrin may be associated with Parkinson's Disease. Dieldrin levels were above normal in brains of people with Parkinson's Disease. Dieldrin adversely affects cellular processes associated with Parkinson's Disease including mitochondrial function and reactive oxygen species production. Dieldrin showed inhibitory effects on proteasome activities at low concentrations. Dieldrin induces apoptosis in dopaminergic neurons via caspase-3-dependent proteolytic activation of protein kinase C delta.

                                                                                                                                                               HYDROCARBONS

Hydrocarbons are organic compounds consisting entirely of hydrogen and carbon. Common sources are : hydrocarbon poisoning such as that of benzene and petroleum usually occurs accidentally by their inhalation or ingestion. Sources of hydrocarbons include : natural gas, cooking gas, petrol, gasoline. People that have been subjected to exposure to petroleum products, especially when working with petroleum products, increase the likelihood of developing Parkinson's Disease. Working in a gas station (petrol station) increased the risk of Parkinson's Disease by 2.6 times.



LEAD

Lead is a chemical element that is toxic in humans. Common sources are : lead contaminated soil, ingestion of lead dust or chips from deteriorating lead-based paints, air pollution from the processing of lead, food grown in contaminated soil, drinking water from plumbing and fixtures that are either made of lead or have trace amounts of lead in them. Lead can also be found in cosmetics in some countries, some herbal remedies, and in toys such as many from China. Serious and chronic exposure to lead can more than double the likelihood of developing Parkinson's Disease. Milder exposure to lead did not increase the likelihood of Parkinson's Disease.


MANEB

The main active element of Maneb is manganese ethylene-bis-dithiocarbamate. Maneb is used as a fungicide. There is a greatly increased likelihood of developing symptoms by people involved in horticulture and agriculture. As Maneb contains manganese it is possible that it causes Parkinson's Disease symptoms via the same means as manganese, which is by inhibiting tyrosine hydroxylation. Tyrosine hydroxylation is essential for the formation of dopamine. It would thereby lower dopamine levels. The effects of Maneb are potentiated when there is simultaneous exposure to the pesticide Paraquat.



MANGANESE

Manganese is a chemical element that is required as a nutrient but can be toxic in large quantities. Occupational exposures occur in welding, when highly exposed, miining as miners are surrounded by manganese dust and airborne manganese particles, alloy production, processing, ferro-manganese operations especially in which manganese ore or manganese compounds are turned into steel, and work with agrochemicals. Areas surrounding manganese heavy industry could also become affected by exposure to manganese. It could occur with very excessive use of manganese supplements. Manganese can cause Manganism, which is a medical disorder that is virtually no different in its symptoms from Parkinson's Disease.



MERCURY

Mercury is a chemical element that is toxic in humans. Common sources are : dietary fish intake, ethnic over-the-counter medications, occupational exposures to mercury vapour, possession of dental amalgam fillings, gold production, skin ointment, and some soaps. One of the chief means of toxicity is via the enzyme pyruvate dehydrogenase (PDH), which is irreversibly inhibited by several mercury compounds. However, the cause of the symptoms of Parkinson's Disease is likely to be due to the fact that mercury potently causes the release of dopamine, thereby lowering dopamine levels.


MPTP

MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine) is a chemical that may be produced accidentally during illicit manufacture of the recreational drug MPPP, which is a synthetic heroin substitute. The most common source is the recreational drug MPPP (Desmethylprodine). It was also developed but unused as a herbicide. It is also an industrial toxin. MPTP inhibits tyrosine hydroxylation, which is essential for the formation of dopamine. So MPTP causes Parkinson's Disease by lowering dopamine levels.


N-HEXANE

N-Hexane is an alkane. Most of the n-hexane used in industry is mixed with solvents. The major use for solvents containing n-hexane is to extract vegetable oils from crops such as soybeans. These solvents are also used as cleaning agents in the printing, textile, furniture, and shoemaking industries. It is also used by chemists. Certain glues used in the roofing and shoe and leather industries also contain n-hexane. Several consumer products contain n-hexane, such as gasoline, spot removers, quick-drying glues used in various hobbies, and rubber cement.


NITROGEN DIOXIDE

Nitrogen dioxide is an intermediate in the industrial synthesis of nitric acid, millions of tons of which are produced each year. At higher temperatures it is a reddish-brown gas that has a characteristic sharp, biting odour and is a prominent air pollutant. Exposure of nitrogen dioxide to tyrosine hydroxylase results in the nitration of its tyrosine residues. High exposure to nitrogen dioxide, largely because of pollution, trebled the risk of Parkinson's Disease. Lower exposures did not significantly increase the risk.



OCTENOL

Octenol, which is commonly known as mushroom alcohol, is produced by several plants and fungi. Octenol can often be inhaled by humans after being produced in damp, mouldy or water damaged buildings. Octenol interferes with two genes involved in the creation of dopamine : the human plasma membrane dopamine transporter (DAT) and the human VMAT ortholog (VMAT2). This demonstrates that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis.


ORGANOPHOSPHOROUS PESTICIDES

Organophosphorous pesticides are used primarily in pest control as alternatives to chlorinated hydrocarbons that can persist in the environment. Organophosphorous pesticides are used in agriculture. Organophosphorus chemicals have also been used as active ingredients in household pesticides for several decades. Organophosphorus pesticides are significantly associated with Parkinson's Disease. The frequent use of household pesticides that contain organophosphorus chemicals increased the chances of developing Parkinson's Disease by 71% .


PARAQUAT

Paraquat is used as a herbicide. There is a greatly increased likelihood of developing symptoms by people involved in horticulture and agriculture. People with Parkinson's Disease are more than twice as likely to report heavy exposure to pesticides over their lifetime as family members without Parkinson's Disease. Those people affected were usually those who used a lot of pesticides in their homes and in their hobbies rather than those who routinely used pesticides for their occupation. Pesticides are also known to affect well water. However, it is claimed that Paraquat only potentiates the effect of Maneb, and that it has no effect on humans on its own.


ROTENONE

Rotenone is used as an insecticide. There is a greatly increased likelihood of developing symptoms by people involved in horticulture and agriculture. People with Parkinson's Disease are more than twice as likely to report heavy exposure to pesticides over their lifetime as family members without Parkinson's Disease. Those affected were usually those who used a lot of pesticides in their homes, rather than those who routinely used pesticides for their occupation. Insecticides are also known to affect well water. Rotenone is commonly used to treat parasitic mites on chickens and other fowl, and so can be found in poultry. Rotenone inhibits tyrosine hydroxylation, which is essential for the formation of dopamine.



TOLUENE

Toluene is used as an octane booster in fuel, as a solvent in paints, paint thinners, chemical reactions, rubber, printing, adhesives, lacquers, leather tanning, disinfectants, producing phenol and TNT. Toluene is also used as a raw material for toluene diisocyanate, which is used in the manufacture of polyurethane foams. Toluene is also used in the manufacture of dyes. Dyes are highly associated with the symptoms of Parkinson's Disease. The means of toxicity is unknown. Toluene has been shown to cause Parkinson's Disease or has been associated with people with Parkinson's Disease.

                                                                                                                                                                                      TRICHLOROETHYLENE

Trichloroethylene is a solvent with a sweet smell that is a clear non-flammable liquid. Trichloroethylene is a solvent that is used in industry and the military and is a common environmental contaminant. It has been used to extract vegetable oils, in coffee decaffeination, and the preparation of flavouring extracts from hops and spices. The means of toxicity is unknown. Workers with workstations adjacent to the source of trichloroethylene and who were subjected to chronic inhalation and dermal exposure from handling trichloroethylene-soaked metal parts all had Parkinson's Disease.

 

 

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