Journal Article

Rotenone, Paraquat, and Parkinson's Disease

Ross, G. Webster, Hoppin, Jane A., Bhudhikanok, Grace S., Chade, Anabel R., Comyns, Kathleen, Goldman, Samuel M., Kasten, Meike, Cambi, Franca, Korell, Monica, Richards, Marie Barber, Langston, J. William, Meng, Cheryl, Umbach, David M., Tanner, Caroline M., Priestley, Benjamin, Kamel, Freya, Fernandez, Hubert H., Marras, Connie, Blair, Aaron, Sandler, Dale P.

2011

Overview

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 whether 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 controlsrone 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 these mechanisms in PD pathophysiology.

• Publisher: National Institute of Environmental Health Sciences,US Department of Health and Human Services
• Subject: Aged / Agriculture / Biological and medical sciences / Case-Control Studies / Chemical hazards / Control equipment / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Development and progression / Environment. Living conditions / Environmental aspects / Environmental health / Epidemiology / Female / Genetics / Health / Health aspects / Herbicides - toxicity / Human / Humans / Insecticides - toxicity / Iowa - epidemiology / Male / Medical sciences / Middle Aged / Mitochondria - metabolism / Nervous system (semeiology, syndromes) / Nervous system as a whole / Neurology / North Carolina - epidemiology / Occupational Exposure / Oxidative Stress / Paraquat / Paraquat - toxicity / Parkinson disease / Parkinson Disease - epidemiology / Parkinson Disease - etiology / Parkinson's disease / Parkinsonian disorders / Parkinsonian Disorders - epidemiology / Parkinsonian Disorders - etiology / Pesticides / Pesticides, fertilizers and other agrochemicals toxicology / Public health. Hygiene / Public health. Hygiene-occupational medicine / Rotenone / Rotenone - toxicity / Stresses / Tanneries / Toxicology