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BACKGROUND: Mitochondrial 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.
OBJECTIVES: Our goal was to determine wherJier pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.
METHODS: We 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.
RESULTS: In 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).
CONCLUSIONS: PD 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 diese mechanisms in PD padiophysiology.
KEY WORDS: aging, agricultural epidemiology, environmental epidemiology, epidemiology, fungicides, herbicides, insecticides, persistent organic pollutants, pesticides. Environ Health Perspect 119:866-872(2011). doi: 10.1289/ehp. 1002839 [Online 26 January 2011]
Mitochondrial dysfunction and oxidative stress have long been implicated as pathophysiologic mechanisms underlying Parkinson's disease (PD) (Betarbet et al. 2000; Di Monte et al. 2002). Genetic forms of PD associated with mutations in the alpha-synuclein, PARKIN, PINK1, of DJ-I genes may involve these mechanisms (Henchcliffe and Beai 2008). In experimental models, the pesticides paraquat, which causes oxidative stress, and rotenone, which inhibits mitochondrial complex I, both induce loss of nigral dopaminergic neurons and behavioral changes associated with human PD (Henchcliffe and Beal 2008). Yet despite decades of laboratory study, neither pesticide has been definitively associated with PD in humans. Previous studies have reported associations with paraquat, but results are inconsistent and, in general, studies included few exposed cases; evidence concerning rotenone is sparse (Table 1). To assess the relevance...