Chlorpyrifos induces apoptosis and necroptosis via the activation of CYP450s pathway mediated by nuclear receptors in LMH cells

Chlorpyrifos (CPF), an organophosphorus pesticide, is detected commonly in environments, where it is thought to be highly toxic to non-target organisms. However, the mechanism of CYP450s pathway mediated by nuclear receptors on CPF-induced apoptosis and necroptosis at the cellular level and the effect of CPF on the cytotoxicity of the chicken hepatocarcinoma cell line (LMH) has also not been reported in detail. Therefore, this experiment aims to explore whether CPF can improve apoptosis and necroptosis in LMH cells by activating the nuclear receptors/CYP450s axis. LMH cells, the subject of this study, were exposed to 5 μg/mL, 10 μg/mL, and 15 μg/mL doses of CPF. With the increase of CPF concentration, the increase of nuclear receptor level led to the up-regulation of CYP450s activity. With the massive production of ROS, the expression of apoptotic pathway genes (Bax, Caspase9, and Caspase3) enhanced, while Bcl-2 expression dropped sharply. The expression of programmed necroptosis genes (RIPK1, RIPK3, and MLKL) heightened, and Caspase8 reduced considerably. In short, our data suggests that excessive activation of nuclear receptors and CYP450s induced by CPF promotes ROS production, which directs apoptosis and programmed necroptosis in LMH cells. Graphical abstract