College of Chemistry Biological Engineering, University of Science and Technology Beijing, No. 30, Xueyuan Road, Beijing, 100083, People's Republic of China.
Environ Sci Pollut Res Int. 2020 Apr;27(12):13726-13734. doi: 10.1007/s11356-019-06869-2. Epub 2020 Feb 7.
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.
阿维菌素在农业和畜牧业中被广泛应用。研究表明，阿维菌素暴露会对非靶标生物产生多种毒性作用，但作用机制尚不清楚。本研究旨在探讨阿维菌素诱导的小鼠胚胎成纤维细胞毒性的作用机制。阿维菌素处理会引起细胞氧化应激（起始浓度为 0.4μg/ml，0.5μM），而 ROS 的过度产生主要是由于阿维菌素对 CAT（起始浓度为 4.4μg/ml，5μM）、SOD（起始浓度为 8.7μg/ml，10μM）、GPx（起始浓度为 4.4μg/ml，5μM）和 GSH 含量（起始浓度为 4.4μg/ml，5μM）活性的影响，这些都是哺乳动物细胞中 ROS 消除途径的重要组成部分。阿维菌素可损害细胞内的 DNA 完整性（如 8-OHdG/dG 比值增加所示），甚至在环境浓度（0.4μg/ml，无观察到不良作用水平）下也是如此，阿维菌素诱导的氧化应激是细胞内发生 DNA 损伤的主要原因之一。此外，JNK 和 ATM/ATR 信号通路抑制剂的预处理可部分挽救细胞活力的降低，表明氧化应激和 DNA 损伤可能参与了阿维菌素诱导的细胞毒性。这些发现可为阿维菌素诱导的细胞毒性作用机制提供新的见解，并有助于更全面地评估阿维菌素的不良影响。
