New insights into crosstalk between apoptosis and necroptosis co-induced by chlorothalonil and imidacloprid in Ctenopharyngodon idellus kidney cells

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 pes-ticides 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 tox-icity on Ctenopharyngodon idellus (grass carp) kidney cell line (CIK cells). Cell death analysis found an obvious in-crease 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-1 alpha signal, the decline of en-ergy 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-1 alpha signal. These data provide new insights for evaluating the stacking interaction and revealing the toxicological effects of pesti-cide mixture. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The co-exposure of chlorothalonil and imidacloprid was found to have synergistic toxicity on grass carp kidney cell line, leading to exacerbated cell death. Additionally, the co-exposure accelerated the inhibition of multiple signaling pathways, significantly affecting the cells.