Hepatotoxicity of N-nitrosodin-propylamine in larval zebrafish by upregulating the Wnt pathway

作者：Ying Wang, Shouqiang Huang, Dagang Wang, Jie Wu, Fasheng Liu, Xinjun Liao, Xiaowen Shi, Juhua Xiao, Shouhua Zhang, Huiqiang Lu · 发表于：Toxicology and Applied Pharmacology · 年份：2024 · DOI：10.1016/j.taap.2024.117132 · 被引用次数：3 · 研究领域：Aldose Reductase and Taurine、Cannabis and Cannabinoid Research、Pancreatic function and diabetes

N-nitrosodin-propylamine is an organic compound mainly used in organic synthesis. As a typical pollutant, the accidental release of N-nitrosodin-propylamine may cause environmental pollution, especially water environment pollution. In the present study, we used the zebrafish model for the first time to evaluate the developmental toxicity of this drug in the liver. Zebrafish larvae fertilized at 72hpf showed a range of toxic responses after 72hpf exposure to the drug. These include increased mortality, delayed absorption of yolk sac nutrients, shorter body length, abnormal liver morphology, gene disruption, and altered expression of various indicators with increasing dose. Studies on the mechanism of toxicity showed that N-nitrosodin-propylamine exposure increased the level of oxidative stress, increased the level of apoptosis in hepatocytes, and up-regulated the transcriptional expression level of Wnt signaling pathway genes. Astaxanthin and IWR-1 can effectively save the liver toxicity in zebrafish caused by N-nitrosodin-propylamine. Our study showed that the drug exposure induced hepatotoxicity in zebrafish larvae through the up-regulation of Wnt signaling pathway, oxidative stress and apoptosis.