Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology,Tongliao,Inner Mongolia, 028000, China; Department of Chemistry and Chemical Engineering, Beijing Forestry University, Beijing, 100083, China.
Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology,Tongliao,Inner Mongolia, 028000, China; Inner Mongolia Minzu Univ, Coll Anim Sci & Technol, Tongliao,Inner Mongolia, 028000, China.
Chemosphere. 2023 Nov;340:139940. doi: 10.1016/j.chemosphere.2023.139940. Epub 2023 Aug 25.
Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.
黄曲霉毒素 B1（AFB1）是一种普遍存在的真菌毒素，会导致各种器官的氧化损伤。目前，对 AFB1 的研究主要集中在其对陆地环境和动物的影响上。然而，其在水生环境和水生动物中的毒性机制尚未得到广泛探索。因此，在本研究中，我们使用斑马鱼作为模型来研究 AFB1 对发育中幼虫肝脏的毒性机制。结果表明，AFB1 暴露抑制了肝脏发育并促进了肝脏脂肪堆积。转录组测序分析显示，AFB1 影响了肝脏的氧化还原代谢和氧化还原酶活性。KEGG 分析表明，AFB1 抑制了谷胱甘肽代谢酶基因途径中 gsto1、gpx4a、mgst3a 和 idh1 的表达，导致肝脏氧化应激。同时，AFB1 还抑制了过氧化物酶和 PPAR 代谢途径中 acox1、acsl1b、pparα、fabp2 和 cpt1 基因的表达，诱导肝脂肪变性和脂质滴积累。抗氧化剂 N-乙酰-L-半胱氨酸（NAC）预处理上调了 gsto1、gpx4a 和 idh1 基因的表达，并改善了 AFB1 诱导的肝脏脂质滴积累。综上所述，AFB1 诱导肝脏氧化应激和脂肪变性，导致肝脏脂肪代谢异常和细胞脂质滴积累。NAC 可用作预防 AFB1 诱导的脂肪堆积的潜在药物。
