Synergistic effects on oxidative stress, apoptosis and necrosis resulting from combined toxicity of three commonly used pesticides on HepG2 cells

The widespread use of pesticides performs a vital role in safeguarding crop yields and quality, providing the opportunity for multiple pesticides to co-exist, which poses a significant potential risk to human health. To assess the toxic effects caused by exposures to individual pesticides (chlorpyrifos, carbofuran and acetamiprid), binary combinations and ternary combinations, individual and combined exposure models were developed using HepG2 cells and the types of combined effects of pesticide mixtures were assessed using concentration addition (CA), independent action (IA) and combination index (CI) models, respectively, and the expression of biomarkers related to oxidative stress, apoptosis and cell necrosis was further examined. Our results showed that both individual pesticides and mixtures exerted toxic effects on HepG2 cells. The CI model indicated that the toxic effects of pesticide mixtures exhibited synergistic effects. The results of the lactate dehydrogenase (LDH) release and apoptosis assay revealed that the pesticide mixture increased the release of LDH and apoptosis levels. Moreover, our results also showed that individual pesticides and mixtures disrupted redox homeostasis and that pesticide mixtures produced more intense oxidative stress effects. In conclusion, we have illustrated the enhanced combined toxicity of pesticide mixtures by in-vitro experiments, which provides a theoretical basis and scientific basis for further toxicological studies. [Display omitted] •Co-existence of multiple pesticides poses potentially greater risk to human health.•CI model showed that the toxic effects of pesticide mixtures exhibited synergistic effects.•Individual pesticides and mixtures disrupted various biological processes on HepG2 cells.•Pesticide mixtures have a synergistic effect on the expression of multiple biomarkers.