Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou 350108, China.
Jimei District Center for Disease Control and Prevention, Xiamen 361022, China.
Toxins (Basel). 2024 Aug 24;16(9):375. doi: 10.3390/toxins16090375.
Aflatoxins belong to a class of mycotoxins, among which aflatoxin B1 (AFB1) has detrimental effects on the health of both animals and humans. It is associated with long-term exposure-induced carcinogenicity, hepatotoxicity, renal toxicity, neurotoxicity, and immunosuppressive properties, resulting in a variety of diseases. The intestine is the first barrier for human exposure to AFB1, but limited investigations have been conducted to clarify the underlying mechanisms of intestinal cytotoxicity. The mechanism of AFB1-induced cytotoxicity was investigated in this study using an integrated approach combining transcriptome, proteome, and metabolome analysis along with molecular dynamics simulation. After exposing SW480 cells to 50 μM AFB1 for 72 h, the transcriptome, proteome, and metabolome exhibited significant enrichment in pathways associated with oxidative stress, fatty acid and lipid metabolism, and glutathione metabolism. The experimental results demonstrated that AFB1 significantly reduces SW480 cells viability, and induces oxidative stress, calcium overload, mitochondrial damage, and lipid metabolism disorders.
黄曲霉毒素属于一类真菌毒素,其中黄曲霉毒素 B1(AFB1)对动物和人类健康有不良影响。它与长期暴露引起的致癌性、肝毒性、肾毒性、神经毒性和免疫抑制特性有关,导致多种疾病。肠道是人体接触 AFB1 的第一道屏障,但对于阐明肠道细胞毒性的潜在机制的研究还很有限。本研究采用转录组、蛋白质组和代谢组学分析结合分子动力学模拟的综合方法,研究了 AFB1 诱导的细胞毒性的机制。在将 SW480 细胞暴露于 50μM AFB1 72 小时后,与氧化应激、脂肪酸和脂质代谢以及谷胱甘肽代谢相关的途径在转录组、蛋白质组和代谢组中表现出明显的富集。实验结果表明,AFB1 显著降低 SW480 细胞活力,并诱导氧化应激、钙超载、线粒体损伤和脂质代谢紊乱。