Metabolomics study reveals DON-induced intestinal toxicity in adult zebrafish through disruption of amino acid metabolism and sphingolipid signaling pathway
Yuxiang Wang , Luhan Wang , Yaowen Du , Feng Yao , Miaomiao Zhao , Chenggang Cai , Ruiyu Zhu , Suqin Shao
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引用次数: 0
Abstract
Deoxynivalenol (DON), a prevalent mycotoxin contaminating cereal crops globally, poses significant threats to animal and human health through its gastrointestinal toxicity. While DON-induced intestinal damage has been documented in mammals, its metabolic mechanisms in aquatic species remain poorly understood, particularly in adult zebrafish models that offer unique advantages for toxicological studies. Multi-omics analysis revealed 16 key differential metabolites (9 upregulated, 7 downregulated) associated with amino acid metabolism and carbohydrate homeostasis. Pathway enrichment analysis identified significant perturbations in 2-oxocarboxylic acid metabolism and sphingolipid signaling, suggesting mitochondrial dysfunction and epithelial barrier disruption as primary toxicity mechanisms. This study establishes the first adult zebrafish model for DON intestinal toxicity evaluation, demonstrating its utility in revealing conserved metabolic targets across species. The identified pathway-specific biomarkers provide novel insights for developing dietary interventions against mycotoxin exposure.
脱氧雪腐镰刀菌烯醇(DON)是一种普遍存在于全球谷类作物中的霉菌毒素,它的胃肠道毒性对动物和人类健康构成严重威胁。虽然哺乳动物中已有关于 DON 引起肠道损伤的记录,但人们对其在水生物种中的代谢机制仍然知之甚少,尤其是在具有独特毒理学研究优势的成年斑马鱼模型中。多组学分析揭示了与氨基酸代谢和碳水化合物平衡相关的 16 个关键差异代谢物(9 个上调,7 个下调)。通路富集分析确定了 2-氧代羧酸代谢和鞘脂信号转导的显著扰动,表明线粒体功能障碍和上皮屏障破坏是主要的毒性机制。这项研究首次建立了用于评估 DON 肠道毒性的成年斑马鱼模型,证明了斑马鱼在揭示跨物种保守代谢靶点方面的实用性。已确定的途径特异性生物标志物为开发针对霉菌毒素暴露的膳食干预措施提供了新的见解。
期刊介绍:
Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems.
Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants
The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.