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.