Transcriptomic profiling provide insights into swainsonine-induced toxic responses and activation of the aryl...

Locoweed refers to poisonous plants in the genus Oxytropis and Astragalus and distributed widely throughout the World. Foraging livestock can be poisoned through ingestion of locoweed resulting in economic loss. Swainsonine is the main toxic component of locoweed and chemically belongs to indolizidine alkaloids. The mechanism of the swainsonine-induced toxic responses is not well understood. In this study, we performed comprehensive transcriptomic analysis examining the differential gene expression in primary renal tubular epithelial cells (RTECs) of rats treated with swainsonine. Our analysis uncovered differential expressions of ncRNA(DEncRNAs) and mRNAs(DEmRNAs) in response to swainsonine treatment. Significant pathways enriched by differential genes through transcriptome association analysis were xenobiotic metabolism-cytochrome P450, bile secretion, and steroid biosynthesis, etc. Notably, aryl hydrocarbon receptor (AhR)-regulated xenobiotic pathway is significantly activated as evidenced by the coordinated up-regulation of the classic AhR-regulated battery of genes Cyp1a1, Cyp1b1, AhRR, Nqo1, and phase II enzyme Gsta2, Gsta3, Gsta5. These results suggest that swainsonine is metabolically detoxified through the AhR regulated xenobiotic detoxification pathway and furthermore, our finding also suggest an intervention strategy to ameliorate to locoweed poisoning through activation of AhR-regulated deoxification pathway.