Document Detail


Organochlorine pesticides dieldrin and lindane induce cooperative toxicity in dopaminergic neurons: role of oxidative stress.
MedLine Citation:
PMID:  20036686     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevated environmental exposure to pesticides has been implicated as a contributing factor in the pathogenesis of Parkinson's disease (PD), a progressive movement disorder resulted from degeneration of the nigrostriatal dopaminergic (DA) pathway. Organochlorine pesticides (OCPs) including dieldrin and lindane remain ubiquitous in the environment and food supply due to their resistance to degradation and bioaccumulation along the food chain. While prior studies have gained insight into the neurotoxic effects of individual OCPs such as dieldrin, the effect of combinations of coexisting OCPs is lacking. In this study, we determined the combined effect of dieldrin and lindane on DA neurons and potential mechanism of action. Combinations of dieldrin and lindane (5-25 microM) were more effective in causing toxicity in immortalized rat N27 DA neurons than when used alone. Mechanistically, dieldrin and lindane combination induced a rapid increase in the levels of intracellular reactive oxygen species, a decrease in mitochondrial membrane potential and activation of caspase 3/7. Pretreatment with antioxidant N-acetyl cysteine blocked the effect of dieldrin and lindane on ROS generation and mitochondrial membrane potential and protected against dieldrin- and lindane-induced neurotoxicity. These results demonstrate that dieldrin and lindane work cooperatively to induce DA neurotoxicity through the induction of oxidative stress and mitochondrial dysfunction. These findings may advance understanding of the role of pesticides in the multi-factorial etiology of PD.
Authors:
Heera Sharma; Ping Zhang; David S Barber; Bin Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-29
Journal Detail:
Title:  Neurotoxicology     Volume:  31     ISSN:  1872-9711     ISO Abbreviation:  Neurotoxicology     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905589     Medline TA:  Neurotoxicology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  215-22     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Animals
Caspases / biosynthesis
Cell Line
Cell Survival / drug effects
Dieldrin / antagonists & inhibitors,  toxicity*
Dopamine / metabolism
Drug Synergism
Glutathione / metabolism
Hydrocarbons, Chlorinated / toxicity*
Lindane / antagonists & inhibitors,  toxicity*
Membrane Potential, Mitochondrial / drug effects
Neurons / drug effects,  metabolism
Oxidative Stress / drug effects*
Pesticides / toxicity*
Rats
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Hydrocarbons, Chlorinated; 0/Pesticides; 0/Reactive Oxygen Species; 58-89-9/Lindane; 60-57-1/Dieldrin; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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