Transcriptomics reveals the mechanism of terbuthylazine-induced nephrotoxicity in chickens: Insights from AMPK/p53-mediated apoptosis perspective

Abstract

As a commonly used pesticide, the widespread use of terbuthylazine (TBA) may cause toxic effects in animals and human. However, the nephrotoxicity induced by TBA is unclear. Here, we explored the mechanism of TBA-induced nephrotoxicity through transcriptomics and molecular biology techniques in broilers. Pathologic analysis showed that TBA could cause renal cell vacuolation and fibrosis in broilers. Additionally, transcriptomic analysis showed that TBA can cause significant changes in the expression of some apoptosis-related genes, and GO and KEGG analysis also found that TBA can significantly change the functions of apoptosis pathway and AMPK signaling pathway in kidney. Subsequently, the protein expression levels of Bax, Bak-1, FADD, and cleaved Caspase-3/Caspase-3 were elevated significantly and the number of TUNEL-positive cells was increased markedly in kidney under TBA exposure. Meanwhile, we also found that TBA could activate AMPK/p53 pathway, as evidenced by the upregulated levels of AMPKα1 phosphorylation and protein expression of p53. Therefore, our results suggested that TBA could induce apoptosis via AMPK/p53 pathway in kidney. These findings identified the nephrotoxic mechanism of TBA through transcriptomics, providing a new insight into TBA toxicology.