Bipyrdyl herbicide -PARAQUAT induced Toxicity and PD
 

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http://tinyurl.com/yoc9ws

also on pubmed

Systemic exposure to paraquat and maneb models early Parkinson's disease in young adult rats.

Cicchetti F, Lapointe N, Roberge-Tremblay A, Saint-Pierre M, Jimenez L, Ficke BW, Gross RE.

Centre de Recherche en Neurosciences, CHUL, RC-9800, 2705 Boulevard Laurier, Sainte-Foy, QC, Canada G1V 4G2. Francesca.Cicchetti@crchul.ulaval.ca

In recent years, several lines of evidence have shown an increase in Parkinson's disease (PD) prevalence in rural environments where pesticides are widely used. Paraquat (PQ--herbicide) and maneb (MB--fungicide) are among the compounds suspected to induce neuronal degeneration and motor deficits characteristics of PD. Here, we investigated the effects of PQ and MB on dopaminergic (DA) neuron-glia cultures and in vivo in young adult rats. In vitro, PQ led to a loss of DA as compared to non-DA neurons and microglial activation in a dose-dependent manner. Addition of MB had no further effect nor did it lead to microglial activation when used alone. In vivo, 2-month old young adult rats were subjected to intraperitoneal injections of vehicle (n = 4), PQ alone (n = 8), or PQ in combination with MB (n = 8) twice a week for 4 weeks and were sacrificed the day following the last injection. Significant loss of nigral DA neurons was observed in both treatment groups, but a significant decrease in striatal DA fibers was not found. Microglial activation was seen in the nigra of rats subjected to PQ with or without MB. Behavioral analyses demonstrated a mixed pattern of motor impairments, which may have been related to early effects of nigral DA neuronal loss or systemic effects associated with MB exposure in addition to PQ. These results indicate that exposure to PQ with or without MB induces neurodegeneration which might occur via an early inflammatory response in young adult animals.

http://www.ncbi.nlm.nih.gov/sites/en...&dopt=Abstract

Toxnet
http://toxnet.nlm.nih.gov/cgi-bin/sis/search

CDC facts about paraquat
 

http://www.bt.cdc.gov/agent/paraquat/basics/facts.asp

Where paraquat is found and how it is used
Paraquat was first produced for commercial purposes in 1961.
Worldwide, paraquat is still one of the most commonly used herbicides.
In the United States, due to its toxicity, paraquat is available for use only by commercially licensed users.

How you could be exposed to paraquat
Paraquat is not known to have been used in any terrorist attacks or wars.
The most likely route of exposure to paraquat that would lead to poisoning is ingestion (swallowing).

ie: on or in our food, vegetables or fruits? :eek:
remember we are what we eat...*

when environment and genes meet - the mix might be PD
 

February 01, 2007
When Environment and Genes Meet, the Mix Might Be Parkinson Disease
Colleen B. Litof


Page 1 of 2

http://appneurology.com/showArticle....leId=197004537



Theories about the causes of Parkinson disease (PD) are as tangled as the neurofilament proteins of Lewy bodies. However, investigators are teasing out threads of evidence that increasingly implicate environmental factors—perhaps aided and abetted by genetics—as contributors to this common neurodegenerative disorder.

Several observations and events have led investigators to speculate that exposure to environmental toxins or pesticides might play a role in PD:

The relative risk of PD is higher in industrialized countries than in nonindustrialized countries.1
PD is more common in agricultural workers than in other groups.1
In the 1980s, an outbreak of severe PD was noted in heroin addicts. The cause was 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP), a contaminant found in synthetic heroin that causes neurochemical, pathologic, and clinical symptoms that resemble those of idiopathic PD. The observations showed that parkinsonism can be chemically induced. However, investigators following MPTP-induced parkinsonism believe that PD pathogenesis is most likely related to a combination of events: the interaction between toxins and genes or exposure to multiple toxins.2,3
Metals, such as iron and copper, have been studied as possible agents of PD development because of their ability to accumulate in the substantia nigra and to also cause oxidative damage. Recent evidence shows that metals interact with a-synuclein and promote its fibrillation in vitro, opening the door to the possibility that they contribute to the formation of Lewy bodies.4 Additional support for the "metal as the bad guy" hypothesis is the discovery that PD is more prevalent in workers with long-term exposure to lead, iron, or copper.5

Numerous epidemiologic studies link pesticide exposure with a high risk of PD.6,7 This relationship appears to be dose-dependent, with the risk for PD increasing with the duration of exposure to pesticides. A study from Taiwan, for instance, found a strong association between exposure to paraquat, an herbicide sprayed on rice fields, and PD. In this study, the risk of PD increased 6-fold in persons exposed to paraquat for more than 20 years.6 Organochlorine and carbamate are other pesticides that have been linked with PD.6

Like metals, the pesticides paraquat and rotenone increase protein fibrillation of α-synuclein.7 The effects of metals and pesticides are additive and are probably mediated through interaction with α-synuclein. This suggests that metals and pesticides may amplify α-synuclein pathology.8,9

Further, viruses may be an environmental trigger for PD. Parkinson-like symptoms have been observed in some persons following influenza-like and herpesvirus infections. Viruses can sometimes cause activation of immune cells and inflammation in the substantia nigra, the area of the brain affected by PD.1

An investigative group from Rush University Medical Center in Chicago inadvertently discovered that exposure to toxins in utero may be a risk factor for PD.10 They found that female rats given lipopolysaccharide during pregnancy gave birth to offspring that had an abnormally low number of dopamine neurons. This neuron loss was accompanied by a reduction in striatal dopamine, an increase in dopamine activity, and increased production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-a)—all features of PD. As in PD, the depletion of dopamine neurons persisted into adulthood and increased as the animals aged. The investigators note that bacterial vaginosis, a common condition in pregnant women, is known to increase the levels of lipopolysaccharide and proinflammatory cytokines in amniotic fluid. Thus, bacterial vaginosis may be a risk factor for PD.

GENETIC FACTORS

Evidence from studies of twins suggests that genetics do not contribute to PD that begins after age 50 years (the most common type), but do contribute to disease that affects younger persons.1 Tanner and colleagues11 examined the occurrence of PD in monozygotic (identical) and dizygotic (nonidentical, 50% shared genes) white male twins. When the diagnosis of PD was made before age 51 years in one twin, PD was 6 times more likely to develop in a monozygotic twin than in a dizygotic twin, but if the first twin had PD diagnosed after the age of 50 years, disease concordance rates were similar in monozygotic and dizygotic pairs.

Data from twin studies have limitations. It can be difficult to estimate disease concordance rates based solely on clinical information. It is possible to have partial degeneration of nigrostriatal tissue and appear clinically normal. Twins could have similar brain lesions, but the rate of progression could differ such that only the most affected sibling shows evidence of disease.2