U Of G Study Uncovers Cause Of Pesticide Exposure Parkinsons Link
A new University of Guelph study has discovered why exposure to pesticides increases some peoples risk of developing Parkinsons disease.
Previous studies have found an association between two commonly used agrochemicals and Parkinsons disease.
Now U of G professor Scott Ryan has determined that low-level exposure to the pesticides disrupts cells in a way that mimics the effects of mutations known to cause Parkinsons disease.
Adding the effects of the chemicals to a predisposition for Parkinsons disease drastically increases the risk of disease onset, said Ryan.
People exposed to these chemicals are at about a 250-per-cent higher risk of developing Parkinsons disease than the rest of the population, said Ryan, a professor in the Department of Molecular and Cellular Biology.
We wanted to investigate what is happening in this susceptible population that results in some people developing the disease.
Used on a variety of Canadian crops, paraquat is used on crops as they grow, and maneb prevents post-harvest spoiling.
Until now, the link between pesticides and Parkinsons disease was based primarily on animal studies as well as epidemiological research that demonstrated an increased risk among farmers and others exposed to agricultural chemicals, said Ryan. We are one of the first to investigate what is happening inside human cells.
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How Environmental Factors Could Cause Parkinsons Disease
Scientists differ about the extent that brain cells are impacted by environmental factors. However, the statistics associated with the disease show that the environment can play a very large role in whether parkinsons disease develops.
Most often, it is exposure to toxic chemicals that could play a role in the development of Parkinsons disease. Usually, these combine with genetic factors to produce the conditions that cause Parkinsons.
Increasing scientific evidence suggests that Parkinsons may be caused by environmental factors such as exposure to herbicides such as Paraquat.
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Rotenone: From Pesticide To Modeling Pd
Among the toxic animal models of PD, rotenone represents one of the most recently used approaches. Rotenone is the most potent member of the rotenoids, a family of natural cytotoxic compounds extracted from various parts of Leguminosa plants. Rotenones chemical structure is presented in .
Chemical structure of rotenone.
In contrast to the 6-OHDA and MPTP models, in rotenone-infused rats, some of the remaining substantia nigra dopaminergic neurons contain proteinaceous inclusions.,, Like LBs in PD, these inclusions are immunoreactive for both ubiquitin and -synuclein, and by electron microscopy they appear composed of a dense core with fibrillar peripheral elements. Likewise in PD in which neurodegeneration extends beyond the dopaminergic system, rotenone infusion is associated with 35% reduction in serotonin transporter density in the striatum, 26% reduction of noradrenergic neurons in the locus coeruleus, and 29% reduction in cholinergic neurons in the pedunculopontine nucleus.
Based on this review, it may be concluded that the chronic administration of rotenone has still a long way to go to become a routine PD model, due to its inconsistent and unpredictable effect on the nigrostriatal pathway. Unless these problems are resolved, it is unlikely that preclinical neuroprotection studies could be carried out successfully in such a model.
How Are People Exposed To Paraquat
Users are exposed to paraquat when they handle the herbicide. Even if they take the necessary precautions, however, other farm workers and nearby residents can be exposed to paraquat through the air. Paraquat can also be transferred onto farm workers clothing, finding its way into peoples homes, where it can wind up on furniture, on carpets and in laundry hampers. It puts entire communities in farm country at risk.
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Why Is Paraquat Restricted
In 2016, the EPA restricted the use of paraquat. The goal was to minimize accidental ingestions and reduce exposure to workers who mix, load, and apply the herbicide. Those restrictions included:
- Requiring changes to the herbicide warning labels to highlight the toxicity and risks associated with paraquat products.
- Restricting use to certified pesticide applicators only. Use by individuals working under the supervision of a certified applicator is also prohibited.
- Requiring specialized training for certified applicators to emphasize that the chemical should neither be transferred to, nor stored in, improper containers.
- Requiring new closed-system packaging to prevent transfer or removal of the pesticide except directly into proper application equipment. This protects users from spills, mixing, pouring the pesticide into other containers, or other actions that could cause exposure.
In October 2020, the EPA proposed new measures to better protect human health and the environment from the dangers of paraquat. The measures include:
Paraquat Weed Killer Found To Be Linked To Parkinsons Disease
The Environmental Protection Agency has found evidence linking exposure to paraquat dichloride, an herbicide colloquially known as paraquat, to the development of Parkinsons disease later in life, per a 2016 regulatory filing. Now, agricultural workers who have been exposed to this toxic chemical may have the right to file lawsuits against paraquat manufacturers for financial compensation.
As reported by the National Law Review, many countries have effectively banned paraquat due to its high level of toxicity. While this toxicity was previously only known in relation to its use in suicides one sip has proven lethal time and again, per reports from The New York Times several journals have recently published peer-reviewed studies showing a link between paraquat and Parkinsons disease. The American Journal of Epidemiology, the Journal of the American Medical Association Neurology, and the National Institute of Environmental Health Sciences are among the reputable sources that have published such findings.
Despite this research, paraquat remains legal to use in the United States even as the same research has compelled dozens of countries around the world to ban this herbicide. Whats worse, the National Water-Quality Assessment Project reported that its use in the U.S. only doubled between 2006 and 2016.
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Treatment: Boosting Dopamines Effects
Your doctor might give you one of these, alone or with another drug:
- Dopamine agonists: They act like dopamine but donât raise levels of it in your brain. You can take them with any drug that has levodopa. You might try pramipexole or ropinirole .
- COMT Inhibitors: They help levodopa last longer. You might get entacapone or tolcapone .
- MAO-B inhibitors: These stop your brain from breaking down levodopa. You could get selegiline or rasagiline .
Early Life Exposures To Pesticides
Animal studies have found evidence that male mice exposed to maneb in utero are at increased risk of developing neurodegeneration if subsequently exposed, as adults, to paraquat. These laboratory findings have led to the speculation that pesticide-exposed children may be at increased risk of PD in later life, although evidence for this association is lacking. Equally, it can be hypothesized that in old age, a pesticide exposure might tip the balance in an individual with pre-existing dopaminergic cell depletion, thus leading to PD. At present, too little is known about the timing of pesticide exposures and the role this may play in the development of PD. A large prospective cohort study of children and their exposure to environmental pesticides is required to study the role of early life pesticide exposures.
Is Surgery An Option
If medicine doesnât work well enough, your doctor may suggest deep brain stimulation . In DBS, your doctor implants electrodes deep in the brain. A device connected to them delivers electrical pulses. Those pulses can help control the tremors caused by Parkinsons.
In the past, doctors sometimes used other operations to damage the brain in ways to help with movement symptoms. But they rarely use those surgeries now.
How Common Is Parkinsons Disease
Approximately 60,000 new cases of Parkinsons disease are diagnosed in the U.S. every year and an estimated 1.5 million people are currently living with the disease. This makes PD somewhat uncommon or even rare compared to other diseases. For example, about 130,000 cases of Alzheimers disease get diagnosed each year. Around 20,000 PD related deaths are recorded annually.
The majority of Parkinsons disease cases develop later in life. Most new cases are diagnosed after age 55. However, a certain percentage of early-onset Parkinsons disease cases occur in people in their 30s and 40s. PD is initially diagnosed based on observation of clinical symptoms and the diagnosis can be confirmed with a PET scan.
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Neurotoxicity Of Pq Mptp And Other Dopamine Congeners
Several studies suggest that systemic administration of PQ can cause neuronal damage and a parkinsonian-like syndrome in experimental animals . The linking mechanism between PQ exposure and Parkinson’s disease is suggested by the alleged chemical similarity between this compound and others known to cause a parkinsonian syndrome, particularly MPTP. MPTP can reproduce most of the biochemical, neuropathological and clinical characteristics of human parkinsonism in both human and non-human primates, with the notable exception of Lewy body formation. MPTP toxicity has been studied in cell systems in mice and in non-human primates. In rats, dopaminergic neurodegeneration is observed at high doses, whereas mice have become the most commonly used species for MPTP studies as they develop a dopaminergic degeneration that may be related to human parkinsonism.
Mechanisms of PQ and MPTP toxicity. PQ can cause an oxidative stress either intracellularly by redox cycling or by activation at cell surfaces by the NADPH oxidase . Mitochondria can be affected indirectly or directly by PQ. In neurons the effects of PQ are believed to be primarily cytosolic. MPTP is converted to its toxic metabolite MPP+ and then sequestered through the dopamine transporter in dopaminergic neurons in which it primarily affects complex I, promoting oxidative stress and mitochondrial damage
It is apparent from this analysis that the initial targets and toxicity mechanisms of PQ and MPP+ differ .
Chemical That Triggers Parkinsons Disease Discovered
- Saint Louis University
- The key brain chemical that causes Parkinsons disease has been discovered. This is a breakthrough finding that could pave the way for new, far more effective therapies to treat one of the most common and debilitating neurological disorders.
Researchers at the Saint Louis University School of Medicine have discovered the key brain chemical that causes Parkinsons disease a breakthrough finding that could pave the way for new, far more effective therapies to treat one of the most common and debilitating neurological disorders.
Currently, the main approach for treating Parkinsons disease, which afflicts more than 1.5 million Americans, is to replace dopamine thats lost when the cells that produce it die off and cause the disorder. With this new research, however, scientists can better work toward neuroprotective therapies those that actually block dopamine cells from dying off in the first place.
We believe this work represents a very significant breakthrough in understanding the complicated chemical process that results in Parkinsons disease, said William J. Burke, M.D., Ph.D., professor of neurology at the Saint Louis University School of Medicine and the studys lead author.
For the first time, weve identified the chemical that triggers the events in the brain that cause this disorder, Burke added. We believe these findings can be used to develop therapies that can actually stop or slow this process.
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The Neurotoxic Herbicide Paraquat
The potent herbicide paraquat is another prototypic toxin known to exert deleterious effects through oxidative stress. Indeed, as reviewed elsewhere, paraquat toxicity is mediated by redox cycling with cellular diaphorase such as nitric oxide synthase, yielding ROS. As detailed, the actual reduction-oxidation cycling reaction of paraquat can thus be depicted in . Thus far, there have been several cases of lethal poisoning resulting from ingestion or dermal exposure. For many years, experimental studies using paraquat were focusing on its effects on lung, liver, and kidney probably because the toxicity induced by this herbicide in these organs is responsible for death after acute exposure. However, significant damage to the brain is seen in individuals who died from paraquat intoxication, despite the fact that paraquat poorly crosses the BBB spontaneously. Furthermore, epidemiological studies have suggested an increased risk for PD due to paraquat exposure, raising the possibility that paraquat could be an environmental parkinsonian toxin. In keeping with this, it is relevant to point out that paraquat exhibits a striking structural similarity to MPTP toxic metabolite 1-methyl-4-pheylpyridinium .
File A Paraquat Parkinson’s Disease Lawsuit
You can file a paraquat Parkinson’s disease lawsuit if previously exposed to the weed killer that resulted in Parkinson’s. Here are some people who are eligible to file paraquat lawsuits:
- People working around commercial pesticides
- Residents in areas near farmlands where paraquat is in use on crops
- Agricultural workers, such as growers, farmers, landscapers, pickers, and licensed applicators
- Any individual diagnosed with Parkinson’s while working or visiting farmland that is sprayed with the herbicide
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Specific Pesticides And Their Link To Pd
The evidence that pesticide use is associated with an increased risk in PD, begs the question are there specific pesticides that are most concerning? When data is collected on this topic in large populations, often the participants in the study are unaware of which specific pesticide exposures they have had. This makes it difficult to determine which pesticides to avoid.
Some studies however were able to investigate the risks of specific chemicals. A recent review summarized the current state of knowledge on this topic. The chemical with the most data linking it to an increased PD risk is paraquat, with exposure associated with a 2-3 fold increased PD risk over the general population.
One particularly comprehensive study investigated exposure to 31 pesticides and their association with PD risk. From that data emerged paraquat and rotenone as the two most concerning pesticides.
- Paraquats mechanism of action is the production of reactive oxygen species, intracellular molecules that cause oxidative stress and damage cells.
- Rotenones mechanism of action is disruption of the mitochondria, the component of the cell that creates energy for cell survival.
Interestingly, both mitochondrial dysfunction and oxidative stress are common themes in our general understanding of what causes death of nerve cells in PD.
Environmental Toxins Linked To Parkinsons
New Studies Support Link Between Chemicals and Parkinsons Disease
Researchers say the findings support evidence of a possible link between environmental toxins and Parkinsons disease and may help explain why some people with genetic risk factors for the disease get it while others do not.
Parkinsons disease is a common neurological disorder that can occur randomly or as the result of inherited gene mutations.
In the study, which appears in Current Biology, researchers looked at fruit flies lacking both forms of a gene that is associated with the inherited form of Parkinsons disease. These specially bred fruit flies became extremely sensitive to the herbicide paraquat and the insecticide rotenone and died after exposure.
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Importance Of Parkinsons Advocacy
Not to be all doom and gloom. This is a serious issue that affects a lot of people with PD and other diseases including myself. Personally, I feel that scientific research is closing in on certain causes for developing PD and the acknowledgment by our government agencies.
I encourage you to be your own advocate. Stand up for your rights to a healthy environment and ask questions of those that include positions of influence and demand answers. Although these are two examples of recognized links to PD, I realize there are other case studies of intentional or unintentional toxic contamination of our environment. If we take action today, we can make the future better for our children and grandchildren.
Risk Of Paraquat Poisoning
This report revealed scientific studies finding that “paraquat increases the likelihood of developing Parkinson’s disease.” In addition, the study found a correlation between the toxic chemical and the increased risk of paraquat poisoning and oxidative stress.
In other research by the same team, farmworkers had an increased risk of developing Parkinson’s disease if exposed to toxic paraquat herbicides for five or more years. This toxic herbicide is widely used and often causes harmful side effects on those exposed to it. Those with Parkinson’s disease should avoid exposure at all costs.
A study conducted in New York as part of the Agricultural Health Study examined whether or not exposure to pesticides, including Paraquat, was connected to Parkinson’s disease.
The study concluded that although there was an association between using the chemical and contracting Parkinson’s disease, other factors might be contributing to this link.
However, that evidence was insufficient to implicate the dangerous chemical as the cause of Parkinson’s disease in humans.
More research is necessary to determine why farmers who use this herbicide are more likely to develop Parkinson’s disease. Still, we know that the link exists due to animal and human studies.
This link between paraquat and Parkinson’s disease should draw serious attention. In addition, farmers should consider using other pesticides that don’t have such harmful side effects.
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Which Pesticides Increase Risk
Pesticides are a broad group of chemicals that are structurally and functionally diverse, they have different actions and potential toxicities. As such, the broad brush approach of previous research which looked for the association between Parkinsons and a variety of chemicals used in agriculture often fails to identify individual chemicals which increase risk.
The chemical with the strongest association is the herbicide paraquat, which has been reported to cause a 2.5 fold increase in the odds of getting Parkinsons. And in the lab, when combined with a chemical fungicide, called maneb, researchers have discovered that exposure may active a toxic inflammatory response, lead to the formation of damaging types alpha-synuclein protein, and cause the loss of dopamine-producing brain cells.
But caution should be taken before suggesting that paraquat can cause Parkinsons directly as a more recent meta-analysis states that the evidence so far cannot fully support a causal link between this chemical and Parkinsons.
Despite this, many countries and the whole of the EU have already banned paraquat, but not for its connection to Parkinsons. The chemical is acutely toxic when inhaled or comes into contact with the skin. In other countries, where it has not been banned, restrictive use measures have been established such as limiting its concentration in formulated products and only allowing licensed mixers and ground applicators to manipulate it.