Abamectin induces cytotoxicity via the ROS, JNK, and ATM/ATR pathways.

Abamectin has been widely used in agriculture and animal husbandry. It has been shown that abamectin exposure could induce multiple toxic effects on non-target organisms, but the underlying mechanism is still largely unknown. In the current study, the mechanism of abamectin-induced cytotoxicity was investigated in mouse embryonic fibroblast cells. Abamectin treatment could cause oxidative stress in cells (beginning at 0.4 μg/ml, 0.5 μM) and the ROS overproduction was mainly induced by the impacts of abamectin on the activities of CAT (beginning at 4.4 μg/mL, 5 μM), SOD (beginning at 8.7 μg/mL, 10 μM), GPx (beginning at 4.4 μg/mL, 5 μM), and contents of GSH (beginning at 4.4 μg/mL, 5 μM), which are important components of the ROS elimination pathway in mammal cells. Abamectin could impair DNA integrity (as demonstrated by increased 8-OHdG/dG ratio) in cells, even at environmental level (0.4 μg/mL, NOAEL), and abamectin-induced oxidative stress was one of the main reasons for the DNA damage that occurred in cells. Moreover, pretreatment with the inhibitor of JNK and ATM/ATR signaling pathway could partially rescue the decreased cell viability, indicating that oxidative stress and DNA damage might be involved in abamectin-induced cytotoxicity. These findings could provide new insights into the mechanism of abamectin-induced cytotoxicity and should be useful for a more comprehensive assessment of the adverse effects of abamectin.