Cadmium-induced apoptosis via ROS/JNK pathway in chicken primary kidney cells and antagonism of taxifolin.

Cadmium (Cd) is a toxic environmental pollutant that can induce reactive oxygen species (ROS)-mediated apoptosis in kidney cells. Taxifolin (Tax), a dihydroflavonol with notable antioxidant activity, has recently attracted attention, but its effect on Cd-induced kidney cell apoptosis remains unclear. This study aimed to investigate the protective mechanism of Tax against Cd-induced apoptosis in chicken primary kidney cells. We combined network pharmacology, network toxicology, and molecular docking to identify potential key targets, and then conducted in vitro verification. We hypothesized that Tax alleviates Cd-induced apoptosis by suppressing oxidative stress and inhibiting the JNK pathway, thereby modulating mitochondrial pathway-related apoptotic genes. AO/EB and Hoechst 33258 staining showed that Tax significantly reduced Cd-induced apoptosis. Detection of antioxidant enzyme mRNA levels and ROS confirmed that Tax alleviated Cd-induced oxidative stress. qRT-PCR and western blotting revealed that Cd activated the JNK pathway and increased expression of pro-apoptotic genes (Bad, Bid, Bax, Bak, DIABLO, Caspase-3, Caspase-9) while decreasing anti-apoptotic genes (Bcl-2, XIAP). Notably, Tax specifically inhibited Cd-induced JNK activation and reversed these apoptotic effects. Molecular docking confirmed interactions between Tax and JNK. The use of the JNK pathway inhibitor SP600125 also further confirmed this view. We conclude that Tax antagonizes Cd-induced apoptosis in chicken primary kidney cells by inhibiting the ROS/JNK pathway and modulating mitochondrial apoptosis-related gene expression.