Triphenyltin-induced hepatotoxicity in zebrafish larvae: A multi-omics insight into lipid metabolism disruption and inflammation

Abstract

Triphenyltin (TPT) is a highly toxic organotin fungicide, widely found in all environments. Previous studies have demonstrated that TPT exposure causes hepatotoxicity and alters lipid profiles in livers and sera, however, the underlying mechanism between TPT-induced dysregulation of lipid metabolism and liver injury remains unclear, prompting us to investigate how TPT disturb lipid metabolic pathways to drive hepatic toxicity. This study used a multi-omics approach to investigate molecular responses associated with TPT-induced liver injury in zebrafish larvae. Zebrafish larvae were exposed to 15, 30 and 60 nmol/L TPT for 72 h. Transgenic zebrafish lines Tg (fabp10a: DsRed) and Tg (lyz: DsRed) were used to observe changes in liver area and inflammatory responses. The structural integrity of the liver was examined using HE staining and transmission electron microscope, while the presence of lipids in the zebrafish was assessed using Oil Red O, Nile Red and Sudan Black B staining. Transcriptomic and metabolomic analyses were conducted using whole-larvae samples to identify molecular pathways associated with the observed liver injury. The results indicate that TPT exposure causes liver inflammation and lipid accumulation. Differentially expressed genes and metabolites were primarily enriched in pathways related to PPAR signaling pathway, fatty acid metabolism and inflammation. RT-qPCR validation showed that changes in the expression of genes related to lipid metabolism were consistent with the omics results. In summary, TPT can cause liver injury in zebrafish by disrupting lipid metabolism and inflammation pathways. This study provides a theoretical basis for elucidating the mechanisms of TPT hepatotoxicity and for assessing the environmental risks of organotin compounds.