Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Department of Pathology, UT southwestern Medical Center, Dallas, TX 75390, United States.
Ecotoxicol Environ Saf. 2021 Jun 1;215:112129. doi: 10.1016/j.ecoenv.2021.112129. Epub 2021 Mar 16.
Avermectin (AVM), as a biological insecticide, is widely used in agriculture and forestry production globally. However, inhalation of AVM may pose a risk, and the lung is the direct target, but the cytotoxicity of AVM on human lung cells is still unclear. Here, we attempted to elucidate the cytotoxic effect and molecular mechanism of AVM on human lung A549 cells. The results indicated that AVM inhibits cell proliferation, and enhances programmed cell death (apoptosis and autophagy). In addition, we found the AVM-treated cells showed an obvious drop in mitochondrial membrane potential and LC3-I/II, increased ROS production, DNA double-strand breaks, caspase-3/9 activated, PARP cleaved, cytochrome c and Bax/Bcl-2 content rise. The results showed that AVM induced mitochondria-related apoptosis and autophagy in lung A549 cells. These results indicate that AVM can pose a potential threat to human health by inducing DNA damage and programmed cell death.
阿维菌素（AVM）作为一种生物杀虫剂，在全球农业和林业生产中得到了广泛应用。然而，吸入 AVM 可能存在风险，肺部是直接靶器官，但 AVM 对人肺细胞的细胞毒性尚不清楚。在这里，我们试图阐明 AVM 对人肺 A549 细胞的细胞毒性作用及其分子机制。结果表明，AVM 抑制细胞增殖，并增强程序性细胞死亡（细胞凋亡和自噬）。此外，我们发现 AVM 处理的细胞线粒体膜电位和 LC3-I/II 明显下降，ROS 产生增加，DNA 双链断裂，caspase-3/9 激活，PARP 切割，细胞色素 c 和 Bax/Bcl-2 含量上升。结果表明，AVM 诱导肺 A549 细胞线粒体相关的细胞凋亡和自噬。这些结果表明，AVM 通过诱导 DNA 损伤和程序性细胞死亡，可能对人类健康构成潜在威胁。
