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膳食黄曲霉毒素B1暴露通过干扰ROS/ERS信号轴诱导淡水鱼(乌鳢)发生炎症和凋亡。

Dietary aflatoxin B1 exposure induced the inflammation and apoptosis in freshwater fish (Channa argus) via disturbing ROS/ERS signaling axis.

作者信息

Jiao Siqi, Shen Zhiqiang, Fang Qiongya, Liu Xiaorui, Hao Yongkun, Kong Yidi, Peng Sibo, Li Min, Wang Guiqin

机构信息

Joint Laboratory of Modern Agricultural Technology International Cooperation, Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, China.

Jilin Academy of Fishery Sciences, Changchun 130033, China.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Oct;296:110227. doi: 10.1016/j.cbpc.2025.110227. Epub 2025 May 18.

DOI:10.1016/j.cbpc.2025.110227
PMID:40393572
Abstract

This study examined the impact of aflatoxin B (AFB) on inflammation and apoptosis within the intestine and head kidney of freshwater fish - northern snakehead (Channa argus), focusing on the interaction between oxidative stress and endoplasmic reticulum stress (ERS) within the signaling pathways. In this study, 600 snakeheads, each weighing approximately 7.52 ± 0.02 g, were categorized into five groups, each consisting of three replicates. These groups were administered diets with incremental concentrations of AFB (0 (CON), 50 (AF1), 100 (AF2), 200 (AF3), and 400 ppb (AF4)) over a duration of eight weeks. Histopathological analysis of the intestine and head kidney showed different degrees of pathological changes in the AFB-added groups. Exposure to AFB markedly elevated ROS levels and activities of enzymes like MDA and 8-OHdG, concurrently decreasing the activities of CAT, GST, SOD, GSH, GPX, and GR within both organs. Additionally, as AFB levels increased, a decrease in the expression of genes associated with antioxidant functions (gst, cat, sod, gsh-px, nqo-1, ho-1, and nrf2) was observed. Analysis via quantitative real-time PCR (qRT-PCR) revealed changes in the mRNA levels of genes related to ERS (grp78, ire1, jnk, perk, chop, and xbp1), apoptosis (cas-3, cas-9, bax, bcl-2, cyt-c, and cas-8), and inflammation (nf-κb, tnf-α, iκbα, il-1β, il-8, and il-6) in both the intestine and head kidney, we found that AFB1 induces overproduction of ROS and exacerbates ERS, thereby activating apoptosis and inflammation. The results underscore the interconnected roles of oxidative stress, ERS, apoptosis, and inflammation in the damage observed in the fish's intestine and head kidney following AFB exposure, indicating that the ROS-ERS signaling axis may play a significant role in the induced inflammation and apoptosis. This study offers valuable insights for further exploration into the effects of AFB and its operational mechanisms in the head kidney and intestine of fish.

摘要

本研究考察了黄曲霉毒素B(AFB)对淡水鱼乌鳢肠道和头肾中炎症及细胞凋亡的影响,重点关注信号通路中氧化应激与内质网应激(ERS)之间的相互作用。本研究中,600条乌鳢,每条重约7.52±0.02克,被分为五组,每组三个重复。这些组在八周的时间内分别投喂含递增浓度AFB(0(对照组)、50(AF1)、100(AF2)、200(AF3)和400 ppb(AF4))的饲料。肠道和头肾的组织病理学分析显示,添加AFB的组出现了不同程度的病理变化。暴露于AFB显著提高了活性氧(ROS)水平以及丙二醛(MDA)和8-羟基脱氧鸟苷(8-OHdG)等酶的活性,同时降低了两个器官中过氧化氢酶(CAT)、谷胱甘肽S-转移酶(GST)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPX)和谷胱甘肽还原酶(GR)的活性。此外,随着AFB水平的升高,观察到与抗氧化功能相关的基因(gst、cat、sod、gsh-px、nqo-1、ho-1和nrf2)表达下降。通过定量实时聚合酶链反应(qRT-PCR)分析发现,肠道和头肾中与ERS(grp78、ire1、jnk、perk、chop和xbp1)、细胞凋亡(cas-3、cas-9、bax、bcl-2、cyt-c和cas-8)以及炎症(nf-κb、tnf-α、iκbα、il-1β、il-8和il-6)相关的基因的mRNA水平发生了变化,我们发现AFB1诱导ROS过量产生并加剧ERS,从而激活细胞凋亡和炎症。结果强调了氧化应激、ERS、细胞凋亡和炎症在AFB暴露后鱼的肠道和头肾所观察到的损伤中的相互关联作用,表明ROS-ERS信号轴可能在诱导的炎症和细胞凋亡中起重要作用。本研究为进一步探究AFB对鱼的头肾和肠道的影响及其作用机制提供了有价值的见解。

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