Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
CCPIA International Trade Committee, China Crop Protection Industry Association, Beijing, 100723, China.
Ecotoxicol Environ Saf. 2019 Nov 15;183:109480. doi: 10.1016/j.ecoenv.2019.109480. Epub 2019 Aug 2.
Spinetoram is one of the most extensively used bio-pesticide in the world. The effects of pesticide in human health are mainly caused by its residue in food. The liver is the direct target of pesticides exposure, however the study of cytotoxicity on human liver cells caused by spinetoram remains unclear. The aim of the present study was to evaluate the cytotoxic effects of the spinetoram in human liver cells in vitro. We demonstrated that spinetoram could inhibit the proliferation of human liver HepG2 cells and induce the oxidative DNA damage. Intracellular biochemical assay indicated that decrease of mitochondrial membrane potential, LC3-II conversion, accumulation of Beclin-1, degradation of p62 and the changes in the phosphorylation of AMPK, mTOR are contributed to the toxic effects of Spinetoram on HepG2 cells. These results showed that the cytotoxicity of spinetoram may be associated with the activity of AMPK/mTOR-mediated autophagy pathway. Meanwhile, the generation of 8-oxodG caused by the spinetoram suggested it has a potential genotoxic effect on human liver cells. We conclude that spinetoram has a significant cytotoxic effect by inducing AMPK/mTOR-mediated autophagy and oxidative DNA damage. This study would provide a theoretical basis for understanding its mechanisms of toxicity and supply an indication for recognizing the safety of spinetoram to human beings.
螺虫乙酯是世界上应用最广泛的生物农药之一。农药对人体健康的影响主要是由其在食物中的残留引起的。肝脏是农药暴露的直接靶器官，然而，螺虫乙酯对人肝细胞的细胞毒性研究尚不清楚。本研究旨在评估螺虫乙酯在人肝癌 HepG2 细胞中的体外细胞毒性。结果表明，螺虫乙酯可抑制人肝癌 HepG2 细胞的增殖并诱导氧化 DNA 损伤。细胞内生化分析表明，线粒体膜电位下降、LC3-II 转化、Beclin-1 积累、p62 降解以及 AMPK、mTOR 磷酸化的变化与螺虫乙酯对 HepG2 细胞的毒性作用有关。这些结果表明，螺虫乙酯的细胞毒性可能与 AMPK/mTOR 介导的自噬途径的活性有关。同时，螺虫乙酯产生的 8-oxodG 表明其对人肝细胞具有潜在的遗传毒性。综上所述，螺虫乙酯通过诱导 AMPK/mTOR 介导的自噬和氧化 DNA 损伤，对 HepG2 细胞具有显著的细胞毒性。本研究为理解其毒性机制提供了理论依据，并为评估螺虫乙酯对人类的安全性提供了依据。
