Document Detail


Reactive oxygen species in in vitro pesticide-induced neuronal cell (SH-SY5Y) cytotoxicity: role of NFkappaB and caspase-3.
MedLine Citation:
PMID:  17189834     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress has been implicated in pesticide-induced neurotoxicity, based on its role in the cascade of biochemical changes that lead to dopaminergic neuronal cell death. We have, therefore, examined the role of oxidative stress caused by the pesticides endosulfan and zineb in human neuroblastoma cells (SH-SY5Y) in culture. Upon treatment with 50-200 microM concentrations of either of these pesticides, SH-SY5Y cells generated both superoxide anion and hydrogen peroxide in a dose-and time-dependent manner. Mixtures of the pesticides significantly enhanced the production of these reactive oxygen species compared to individual pesticide exposures. Pesticide treatment decreased superoxide dismutase, glutathione peroxidase, and catalase activities in SH-SY5Y cells. Additionally, these pesticides induced lipid peroxide (thiobarbituric acid reactive products) formation in these cells. While both pesticides individually (at 100 microM) increased caspase-3 activity, cells exposed to a mixture of the pesticides exhibited significantly low levels of this enzyme, probably due to excessive necrotic cell death. Furthermore, exposure to these pesticides increased nuclear NFkappaB activity. Taken together, these findings suggest that the cytotoxicity of endosulfan and zineb, both individually and in mixtures may, at least in part, be associated with the generation of reactive oxygen species with concomitant increased expression of NFkappaB.
Authors:
Zhenquan Jia; Hara P Misra
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2006-10-28
Journal Detail:
Title:  Free radical biology & medicine     Volume:  42     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-26     Completed Date:  2007-02-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  288-98     Citation Subset:  IM    
Affiliation:
Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, 2265 Kraft Drive, Blacksburg, VA 24060, USA.
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MeSH Terms
Descriptor/Qualifier:
Caspase 3 / drug effects*,  metabolism
Cell Line, Tumor
Dose-Response Relationship, Drug
Endosulfan / toxicity
Enzyme-Linked Immunosorbent Assay
Humans
Hydrogen Peroxide / metabolism
NF-kappa B / drug effects*,  metabolism
Neurons / drug effects*
Oxidative Stress / physiology
Pesticides / toxicity*
Reactive Oxygen Species / metabolism*
Superoxides / metabolism
Time Factors
Zineb / toxicity
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/Pesticides; 0/Reactive Oxygen Species; 11062-77-4/Superoxides; 115-29-7/Endosulfan; 12122-67-7/Zineb; 7722-84-1/Hydrogen Peroxide; EC 3.4.22.-/Caspase 3

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


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