A high-throughput liver-kidney metabolic interaction chip for insights into the nephrotoxicity mechanisms of triptolide

conditions. Notably, a TPL-induced elevation in urea was observed only in the HLKOC, demonstrating the superior sensitivity of the liver-kidney co-culture. Multi-omics analysis revealed that TPL induced distinct metabolic and transcriptional responses in the HLKOC, involving pathways related to linoleic acid metabolism and vesicle-mediated processes, and led to the significant downregulation of transport proteins cubilin and GLUT1. These findings highlight the advantages of the HLKOC over single-organ systems for drug toxicity assessment and provide new insights into the mechanisms of TPL-induced nephrotoxicity.