Transport and Combined Cytotoxicity of Tebuconazole and Prochloraz Residues from Tomato and Grape in an Intestinal Caco-2 Cell Model

Monitoring for tebuconazole and prochloraz residues in 99 tomato and grape samples showed a relatively high detection rate (48.48-65.66%), highlighting the need to investigate their mixture interactions during intestinal absorption. Herein, Caco-2 cell monolayers were used to investigate the transepithelial transport of tebuconazole and prochloraz. Results showed that coexposure increased tebuconazole and prochloraz transport by 1.62- and 0.72-fold, respectively, compared with single exposure. Molecular docking indicated that both pesticides formed strong hydrogen bonds with organic anion transporters. Examining transporter-mediated transport further revealed that prochloraz synergized with P-glycoprotein to inhibit tebuconazole efflux. Co-exposure also exacerbated cytotoxicity and oxidative stress, particularly reactive oxygen species and glutathione. Transcriptomic analysis confirmed the downregulation of ABC and SLC transporter genes and the enrichment of pathways related to oxidative stress. These results indicate that mixtures of tebuconazole and prochloraz disrupt transporter-mediated absorption and exert synergistic oxidative damage.