The formulation of most pesticides is proprietary and individual components are therefore not generally known. In a preliminary study, we identified six compounds that are often present in pesticides, of which 4-nonyl...The formulation of most pesticides is proprietary and individual components are therefore not generally known. In a preliminary study, we identified six compounds that are often present in pesticides, of which 4-nonylphenyl-polyethylene glycol （NP-40） was found to be the most toxic. In this study, we investigated the toxicity of NP-40 and underlying mechanism in neuronal SK-N-SH cells. Exposure to NP 40 at concentrations higher than 60 μmol/L for 24 hr decreased cell viability. The cytotoxicity of NP-40 was time- and concentration-dependent. Nuclear fragmentation and chromatin condensation were apparent starting at 50 μmol/L NP-40, and increased at higher concentrations. The expression of apoptotic factors including p53 and B-cell lymphoma （Bcl）-2-associated X protein was upregulated, while that of the anti-apoptotic marker Bcl-2 was downregulated at 80 μmol/L NP-40. Cytochrome c release was observed from 80 to 100 μmol/L by confocal microscopy. Caspase-9 and -3/7 activities increased according to concentration, and fluorescence-activated cell sorting analysis showed that apoptosis was induced at 50 μmol/L and was increased at 80 μmol/L. Our findings indicate that NP-40 stimulates the mitochondrial-mediated apoptosis pathway and reactive oxygen species production in a concentration-dependent manner, and suggest that antioxidant administration may be an effective treatment for patients with acute NP-40 poisoning.展开更多
基金supported by the Cooperative Research Program for Agriculture Science and Technology Development of the Rural Development Administration,South Korea(Project no.PJ01083201)
文摘The formulation of most pesticides is proprietary and individual components are therefore not generally known. In a preliminary study, we identified six compounds that are often present in pesticides, of which 4-nonylphenyl-polyethylene glycol （NP-40） was found to be the most toxic. In this study, we investigated the toxicity of NP-40 and underlying mechanism in neuronal SK-N-SH cells. Exposure to NP 40 at concentrations higher than 60 μmol/L for 24 hr decreased cell viability. The cytotoxicity of NP-40 was time- and concentration-dependent. Nuclear fragmentation and chromatin condensation were apparent starting at 50 μmol/L NP-40, and increased at higher concentrations. The expression of apoptotic factors including p53 and B-cell lymphoma （Bcl）-2-associated X protein was upregulated, while that of the anti-apoptotic marker Bcl-2 was downregulated at 80 μmol/L NP-40. Cytochrome c release was observed from 80 to 100 μmol/L by confocal microscopy. Caspase-9 and -3/7 activities increased according to concentration, and fluorescence-activated cell sorting analysis showed that apoptosis was induced at 50 μmol/L and was increased at 80 μmol/L. Our findings indicate that NP-40 stimulates the mitochondrial-mediated apoptosis pathway and reactive oxygen species production in a concentration-dependent manner, and suggest that antioxidant administration may be an effective treatment for patients with acute NP-40 poisoning.
