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• W2951397983 abstract "The widespread use of abamectin has recently raised safety concerns as abamectin has yielded various toxicities to non-target organisms. However, the underlying mechanisms of abamectin-induced toxicity are still largely unknown. The present study aimed to investigate the abamectin-induced cytotoxicity in mouse macrophage cells (RAW264.7) and its underlying mechanisms. Abamectin treatment caused oxidative stress as characterized by increased intensity of the ROS indicator. Abamectin also led to DNA damage as demonstrated by increased 8-OHdG/dG ratio in cells even at a relatively low dose (NOAEL). Pretreatment with catalase-PEG, a ROS inhibitor, attenuated abamectin-induced DNA damage, indicating that ROS overproduction should be the reason for abamectin-induced DNA damage. The effects of abamectin on ROS elimination and generation were also investigated, and the results showed that abamectin induced concentration-dependent alteration in the expression and activities of CAT, SOD, GPx enzymes and GSH level (ROS elimination), but had limited effects on the expression and activities of NOX, mitochondrial complex I and III (ROS production) in RAW264.7 cells. Therefore, the effects of abamectin on ROS elimination should be the main reason for abamectin-induced oxidative stress in RAW264.7 cells. Abamectin treatment activated MAPK and ATM/ATR signaling pathways as demonstrated by increased phosphorylation of JNK, ATM and ATR. In addition, inhibiting JNK and ATM/ATR signaling pathways partially rescued the decrease in cell viability, indicating that abamectin-induced ROS overproduction and DNA damage might finally lead to cytotoxicity through JNK and ATM/ATR signaling pathways. These findings should be useful for the more comprehensive assessment of the toxic effects of abamectin." @default.
• W2951397983 created "2019-06-27" @default.
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• W2951397983 date "2019-11-01" @default.
• W2951397983 modified "2023-10-11" @default.
• W2951397983 title "ROS generation and DNA damage contribute to abamectin-induced cytotoxicity in mouse macrophage cells" @default.
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• W2951397983 doi "https://doi.org/10.1016/j.chemosphere.2019.06.031" @default.
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