New insights into crosstalk between apoptosis and necroptosis co-induced by chlorothalonil and imidacloprid in Ctenopharyngodon idellus kidney cells
2021
Li, Xiaojing | Zhao, Xia | Yao, Yujie | Guo, Mengyao | Li, Shu
Overuse and co-exposure of pesticides have become a public health problem and threat seriously water health and environmental organisms and even humans. Chlorothalonil (CT) and imidacloprid (IMI) are high-selling pesticides worldwide, which can persist in the environment, and present a series of severely toxic effects on non-target animals. However, the effect of co-application on aquatic organisms is unknown. Based on the concept of the toxic unit (TU), toxic interaction of CT and IMI was evaluated and showed the additive and synergistic toxicity on Ctenopharyngodon idellus (grass carp) kidney cell line (CIK cells). Cell death analysis found an obvious increase of the apoptosis and necrosis rates exposed to CT and IMI, and aggravation when applied together. Moreover, CT and IMI co-exposure accelerated the inhibition of CYP450s/ROS/HIF-1α signal, the decline of energy metabolism, mitochondrial dynamics disorder, activation of Bcl2/Bax/Cyt C/Casp3/Casp9 pathway and RIP1/RIP3/MLKL pathway. Bioinformatics analysis showed autophagy, cell response, NOD-like receptor signaling pathway might be affected by co-exposure. In summary, the above results indicate that co-exposure to CT and IMI has synergistic toxicity and aggravates cell death via inhibition of the CYP450s/ROS/HIF-1α signal. These data provide new insights for evaluating the stacking interaction and revealing the toxicological effects of pesticide mixture.
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