Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

Kuter, Katarzyna; Nowak, Przemysław; Gołembiowska, Krystyna; Ossowska, Krystyna

doi:10.1007/s11064-010-0163-x

Cited by 45 publications

(35 citation statements)

References 47 publications

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“…Multiple but sufficiently low doses of PQ are well tolerated by peripheral organs in rats without apparent oxidative stress [44]. In the present study, ROS levels increased (as reflected by high activity of ROS-scavenging enzymes) significantly in three regions of brain with PQ doses of 10 mg/kg b.w.…”

Section: Discussionsupporting

confidence: 54%

Differential regional expression patterns of α-synuclein, TNF-α, and IL-1β; and variable status of dopaminergic neurotoxicity in mouse brain after Paraquat treatment

Mitra

Chakrabarti

Bhattacharyya

2011

J Neuroinflammation

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BackgroundParaquat (1, 1-dimethyl-4, 4-bipyridium dichloride; PQ) causes neurotoxicity, especially dopaminergic neurotoxicity, and is a supposed risk factor for Parkinson's disease (PD). However, the cellular and molecular mechanisms of PQ-induced neurodegeneration are far from clear. Previous studies have shown that PQ induces neuroinflammation and dopaminergic cell loss, but the prime cause of those events is still in debate.MethodsWe examined the neuropathological effects of PQ not only in substantia nigra (SN) but also in frontal cortex (FC) and hippocampus of the progressive mouse (adult Swiss albino) model of PD-like neurodegeneration, using immunohistochemistry, western blots, and histological and biochemical analyses.ResultsPQ caused differential patterns of changes in cellular morphology and expression of proteins related to PD and neuroinflammation in the three regions examined (SN, FC and hippocampus). Coincident with behavioral impairment and brain-specific ROS generation, there was differential immunolocalization and decreased expression levels of tyrosine hydroxylase (TH) in the three regions, whereas α-synuclein immunopositivity increased in hippocampus, increased in FC and decreased in SN. PQ-induced neuroinflammation was characterized by area-specific changes in localization and appearances of microglial cells with or without activation and increment in expression patterns of tumor necrosis factor-α in the three regions of mouse brain. Expression of interleukin-1β was increased in FC and hippocampus but not significantly changed in SN.ConclusionThe present study demonstrates that PQ induces ROS production and differential α-synuclein expression that promotes neuroinflammation in microglia-dependent or -independent manners, and produces different patterns of dopaminergic neurotoxicity in three different regions of mouse brain.

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Section: Discussionsupporting

confidence: 54%

Differential regional expression patterns of α-synuclein, TNF-α, and IL-1β; and variable status of dopaminergic neurotoxicity in mouse brain after Paraquat treatment

Mitra

Chakrabarti

Bhattacharyya

2011

J Neuroinflammation

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“…Experimentally, paraquat produces subcellular changes associated with PD, including increased production of reactive oxygen species, alpha-synuclein aggregation, and selective nigral injury (Dinis-Oliveira et al 2006; Kuter et al 2010; McCormack et al 2002). Previously, we found an association between paraquat use and PD in prevalent but not incident self-reported cases in the AHS (Kamel et al 2007) and a nonsignificant association between PD and occupational paraquat use in a multicenter case–control study (Tanner et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Rotenone, Paraquat, and Parkinson’s Disease

Tanner

Kamel

Ross

et al. 2011

Environ Health Perspect

1,195

806

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BackgroundMitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.ObjectivesOur goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.MethodsWe assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case.ResultsIn 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7).ConclusionsPD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.

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“…[36][37][38] In experimental animal studies, paraquat exposure can induce reactive oxygen species production in the brain, which may lead to loss of nigral dopaminergic neurons. 39,40 This, combined with recent experimental animal data, 12 suggests that the physiologic process triggered by a head injury may increase the vulnerability of neurons to insults from neurotoxic pesticides, with the combination increasing the risk of PD more than each exposure on its own.…”

Section: Figurementioning

confidence: 99%

Traumatic brain injury, paraquat exposure, and their relationship to Parkinson disease

et al. 2012

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Objectives: Traumatic brain injury (TBI) increased risk of Parkinson disease (PD) in many but not all epidemiologic studies, giving rise to speculations about modifying factors. A recent animal study suggested that the combination of TBI with subthreshold paraquat exposure increases dopaminergic neurodegeneration. The objective of our study was to investigate PD risk due to both TBI and paraquat exposure in humans.Methods: From 2001 to 2011, we enrolled 357 incident idiopathic PD cases and 754 population controls in central California. Study participants were asked to report all head injuries with loss of consciousness for .5 minutes. Paraquat exposure was assessed via a validated geographic information system (GIS) based on records of pesticide applications to agricultural crops in California since 1974. This GIS tool assesses ambient pesticide exposure within 500 m of residences and workplaces.Results: In logistic regression analyses, we observed a 2-fold increase in risk of PD for subjects who reported a TBI (adjusted odds ratio [AOR] 2.00, 95% confidence interval [CI] 1.28-3.14) and a weaker association for paraquat exposures (AOR 1.36, 95% CI 1.02-1.81). However, the risk of developing PD was 3-fold higher (AOR 3.01, 95% CI 1.51-6.01) in study participants with a TBI and exposure to paraquat than those exposed to neither risk factor.Conclusions: While TBI and paraquat exposure each increase the risk of PD moderately, exposure to both factors almost tripled PD risk. These environmental factors seem to act together to increase PD risk in a more than additive manner. Neurology Parkinson disease (PD), the second most common neurodegenerative disorder affecting 1%-2% of the population over 65 years of age, is characterized by progressive loss of dopamine neurons in substantia nigra pars compacta, leading to bradykinesia, rigidity, postural instability, and resting tremor as the cardinal motor features. It is widely acknowledged that PD etiology is most likely multifactorial. Lifestyle habits such as smoking and caffeine intake, genetic polymorphisms, environmental exposures to pesticides or metals, long-term exposure to certain medications, and interactions between these factors collectively appear to contribute to disease development. We have previously reported 2-to 3-fold increases in risk of developing PD when exposed to specific types or classes of pesticides, especially for combined exposures to paraquat and maneb, and for patients who carry genetic polymorphisms in susceptibility genes. 1,2 In the past 20 years, many but not all studies of traumatic brain injury (TBI) have linked head injuries with or without loss of consciousness to PD. [3][4][5][6][7][8][9][10] We speculated that TBI may require additional risk or susceptibility factors in order to cause PD, which has sometimes been referred

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Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

Cited by 45 publications

References 47 publications

Differential regional expression patterns of α-synuclein, TNF-α, and IL-1β; and variable status of dopaminergic neurotoxicity in mouse brain after Paraquat treatment

Differential regional expression patterns of α-synuclein, TNF-α, and IL-1β; and variable status of dopaminergic neurotoxicity in mouse brain after Paraquat treatment

Rotenone, Paraquat, and Parkinson’s Disease

Traumatic brain injury, paraquat exposure, and their relationship to Parkinson disease

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