黄曲霉毒素B1通过调节氧化应激和开启线粒体凋亡途径,引发兔肝细胞的凋亡。
Aflatoxin B1 triggers apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway.
发表日期:2023 Sep 14
作者:
Lu Zhang, Shaowen Shi, Ying Liu, Yuqing Cui, Yixuan Zhu, Yongzhan Bao, Baojiang Chen, Wanyu Shi
来源:
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
摘要:
黄曲霉毒素B1(AFB1)被认为是最有毒的致癌化合物,接触AFB1与肝细胞癌高度相关。本研究旨在调查不同剂量AFB1对兔生长性能和肝脏的影响,并探索其潜在机制。共80只30天龄肉兔随机分为四个处理组。对照组饲喂无污染饲料,AFL组、AFM组和AFH组分别饲喂含有13μg/kg、19μg/kg和25μg/kg AFB1的污染饲料。结果显示,AFB1对兔的生产性能有害影响,导致体重增长减少。此外,AFB1暴露与血清中谷草转氨酶(AST)和丙丙氨酸转氨酶(ALT)活性增加、总蛋白(TP)和白蛋白(ALB)水平降低相关。AFB1诱导了肝组织中活性氧(ROS)和丙二醛(MDA)的产生,同时抑制了谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性。AFB1降低了核因子红细胞2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)和NAD(P)H脱氢醌-1(NQO-1)的mRNA转录和蛋白质表达水平。AFB1不仅降低了肝脏中细胞色素P4501A2(CYP1A2)、细胞色素P4502A6(CYP2A6)和细胞色素P4503A4(CYP3A4)的含量,还增加了肝脏中AFB1-DNA加合物的含量。此外,AFB1增强了细胞色素c(cyt-c)、卡斯蛋白-9、卡斯蛋白-3和Bcl-2相关X蛋白(Bax)的表达,同时抑制了B细胞淋巴瘤2蛋白(Bcl-2)的表达。因此,我们证明AFB1通过调节氧化应激和启动线粒体凋亡途径在兔肝细胞中触发了凋亡,并降低了兔的性能。版权所有 © 2023,由Elsevier Inc.发布。
Aflatoxin B1 (AFB1) is considered the most toxic carcinogenic compound, and exposure to AFB1 is highly associated with hepatocellular carcinoma. The aim of this study was to investigate the effects of different doses of AFB1 on growth performance and the liver of rabbits, as well as explore its underlying mechanisms. A total of eighty 30-day-old meat rabbits were randomly divided into four treatments. The control group was fed a pollution-free diet, while the AFL, AFM, and AFH groups were fed contaminated diets containing 13 μg/kg, 19 μg/kg, and 25 μg/kg of AFB1, respectively. The results showed that AFB1 had detrimental effects on the production performance of rabbits, resulting in decreased weight gain. Additionally, AFB1 exposure was associated with increased activity of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT), as well as decreased levels of total protein (TP) and albumin (ALB) in the serum. AFB1 induced the production of reactive oxygen species (ROS) and malondialdehyde (MDA) while inhibiting the activity of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activity in liver tissues. AFB1 decreased the mRNA transcription and protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone-1 (NQO-1). AFB1 not only decreased the contents of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6) and cytochrome P4503A4 (CYP3A4) but also increased the content of AFB1-DNA adducts in the liver. Furthermore, AFB1 enhanced the expression of cytochrome c (cyt-c), caspase-9, caspase-3, and Bcl-2-associated X protein (Bax), while inhibiting the expression of B-cell lymphoma 2 (Bcl-2). Therefore, we demonstrated that AFB1 triggered apoptosis in rabbit hepatocytes via mediating oxidative stress and switching on the mitochondrial apoptosis pathway, and decreased rabbit performance.Copyright © 2023. Published by Elsevier Inc.