Reactive oxygen species in in vitro pesticide-induced neuronal cell (SH-SY5Y) cytotoxicity: Role of NF?B and caspase-3

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Zhenquan Jia, Assistant Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: 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 µM 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 µM) 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 NF?B 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 NF?B.

Additional Information

Free Radical Biology and Medicine 42(2):288-298
Language: English
Date: 2007
Pesticides, Neuronal cell, Endosulfan, Zineb, Reactive oxygen species, Oxidative stress, Caspase-3, NF?B, Superoxide dismutase, Catalase, Glutathione peroxidase, Free radicals

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