A preliminary study of combined toxicity and underlying mechanisms of imidacloprid and cadmium coexposure using a multiomics integration approach

IF 4.6 3区 医学 Q1 PHARMACOLOGY & PHARMACY Toxicology Pub Date : 2025-02-01 Epub Date: 2025-01-21 DOI:10.1016/j.tox.2025.154063
Yuankai Wang , Ziyue Zhuang , Guangyun He , Zsolt Zalán , Hui Shi , Muying Du , Jianquan Kan , Tian Cai , Kewei Chen
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Abstract

Imidacloprid (IMI) and cadmium (Cd) have been shown to be harmful to mammals separately, but their combined toxicity to mammals remains largely unknown. In this study, biochemical analysis (oxidative stress and serum indicators of liver and kidney function), pathological sections and multiomics (metabolomics and transcriptomics) methods were used to investigate the changes and mechanisms of liver and kidney in mice coexposed to IMI and Cd. Biochemical analysis and pathological section results showed that oxidative stress, organ function, and cell damage were aggravated after the combination of the two methods. Omics results revealed the following mechanism: When mouse liver and kidney cells were threatened by the external environment, mitochondrial DNA was inhibited, which leads to changes in energy metabolism. In this process, lipid metabolism and amino acid metabolism were disordered, resulting in the inhibition of substances related to lipid metabolism and amino acid metabolism that protect the body from oxidative damage, and then showed more serious liver and kidney oxidative stress and liver and kidney function and cell damage. This research offers novel insights for the assessment of the safety profile associated with the concurrent exposure of the two chemicals in mammalian species.
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使用多组学整合方法对吡虫啉和镉共暴露的联合毒性和潜在机制进行初步研究。
吡虫啉(IMI)和镉(Cd)已分别被证明对哺乳动物有害,但它们对哺乳动物的综合毒性在很大程度上仍然未知。本研究采用生化分析(氧化应激和肝肾血清指标)、病理切片和多组学(代谢组学和转录组学)方法研究IMI和Cd共暴露小鼠肝脏和肾脏的变化及其机制。生化分析和病理切片结果表明,两种方法联合后,氧化应激、器官功能和细胞损伤均加重。组学结果揭示了以下机制:当小鼠肝脏和肾脏细胞受到外界环境威胁时,线粒体DNA受到抑制,导致能量代谢发生变化。在此过程中脂质代谢和氨基酸代谢紊乱,导致保护机体免受氧化损伤的脂质代谢和氨基酸代谢相关物质受到抑制,进而表现出较为严重的肝肾氧化应激和肝肾功能及细胞损伤。这项研究为哺乳动物同时接触这两种化学物质的安全性评估提供了新的见解。
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来源期刊
Toxicology
Toxicology 医学-毒理学
CiteScore
7.80
自引率
4.40%
发文量
222
审稿时长
23 days
期刊介绍: Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.
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