Spinetoram confers its cytotoxic effects by inducing AMPK/mTOR-mediated autophagy and oxidative DNA damage

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.