Synergistic microglial reactive oxygen species generation induced by pesticides lindane and dieldrin.
Elevated environmental exposure to pesticides is a known risk factor to the development of sporadic Parkinson's disease resulting from the degeneration of nigral dopamine neurons. Among the suspected agents are the highly persistent and bioaccumulative organochlorinated pesticides (OCPs). We report here that lindane and dieldrin, two widely present OCPs that are found enriched in the nigra of postmortem Parkinson's disease brains synergistically induced the production of reactive oxygen species (ROS) in microglia. Inhibitor studies indicated that the lindane and dieldrin-induced ROS generation was mediated by NADPH oxidase. As microglial ROS is a key contributor to the degeneration of the oxidative damage-vulnerable dopamine neurons, our findings shed significant light on the role of OCPs in the development of Parkinson's disease.
Mao
Haoyu
H
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Liu
Bin
B
D000818:Animals; D002460:Cell Line; D004026:Dieldrin / Q000633:toxicity*; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000633:toxicity; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D004785:Environmental Pollutants; D007306:Insecticides; D017382:Reactive Oxygen Species; D001556:Hexachlorocyclohexane; D019255:NADPH Oxidases; D004026:Dieldrin