Permethrin exposure impacts zebrafish lipid metabolism via the KRAS-PPAR-GLUT signaling pathway, which is mediated by oxidative stress

IF 4.1 2区 环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY
Afrasyab Khan, Bibimaryam Khan, Shakeel Hussain, Yuhan Wang, Weijun Mai, Yongzhong Hou
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Abstract

Permethrin (Per) is a widely used and frequently detected pyrethroid pesticide in agricultural products and the environment. It may pose potential toxicity to non-target organisms. Per has been reported to affect lipid homeostasis, although the mechanism is undefined. This study aims to explore the characteristic transcriptomic profiles and clarify the underlying signaling pathways of Per-induced lipid metabolism disorder in zebrafish liver. The results showed that environmental exposure to Per caused changes in the liver index, histopathology, and oxidative stress in zebrafish. Moreover, transcriptome results showed that Per heavily altered the pathways involved in metabolism, the immune system, and the endocrine system. We conducted a more in-depth analysis of the genes associated with lipid metabolism. Our findings revealed that exposure to Per led to a disruption in lipid metabolism by activating the KRAS-PPAR-GLUT signaling pathways through oxidative stress. The disruption of lipid homeostasis caused by exposure to Per may also contribute to obesity, hepatitis, and other diseases. The results may provide new insights for the risk of Permethrin to aquatic organisms and new horizons for the pathogenesis of hepatotoxicity.

Abstract Image

接触氯菊酯会通过KRAS-PPAR-GLUT信号通路影响斑马鱼的脂质代谢,而这种影响是由氧化应激介导的。
氯菊酯(Per)是一种广泛使用的拟除虫菊酯杀虫剂,在农产品和环境中经常被检测到。它可能会对非目标生物产生潜在毒性。有报道称,Per 会影响脂质稳态,但其机制尚不明确。本研究旨在探索 Per 诱导斑马鱼肝脏脂质代谢紊乱的转录组特征,并阐明其潜在的信号通路。结果表明,环境暴露于Per会引起斑马鱼肝脏指数、组织病理学和氧化应激的变化。此外,转录组结果表明,Per 严重改变了涉及代谢、免疫系统和内分泌系统的通路。我们对与脂质代谢相关的基因进行了更深入的分析。我们的研究结果表明,暴露于 Per 会通过氧化应激激活 KRAS-PPAR-GLUT 信号通路,从而导致脂质代谢紊乱。暴露于 Per 引起的脂质平衡紊乱也可能导致肥胖、肝炎和其他疾病。研究结果可能会为菊酯对水生生物的风险提供新的见解,并为肝毒性的发病机制提供新的视野。
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来源期刊
Aquatic Toxicology
Aquatic Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
4.40%
发文量
250
审稿时长
56 days
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.
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