基于蛋白质代谢组学分析的甲醛诱导肝毒性表征

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2025-09-02 DOI:10.1016/j.toxlet.2025.09.003

Sanjita Paudel , Hyunchae Sim , Eunjoo Kang , Minseo Kim , Chai Won Park , Ann-yae Na , Eun Ki Min , Ki-Tae Kim , Wonhwa Lee , Sangkyu Lee

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引用次数: 0

摘要

甲醛（FA）是一种众所周知的环境有毒物质，用于各种行业，包括生物医学、农业和纺织，但对健康构成重大风险。尽管进行了广泛的研究，FA的确切肝毒性机制仍不清楚。本研究通过对大鼠模型进行蛋白质组学和代谢组学的综合分析，研究了fa诱导的肝毒性，鉴定出84种差异表达蛋白和66种代谢物。使用xMWAS和Reactome软件，研究强调铁下垂是fa诱导肝损伤的关键途径。STAT3/HO-1被认为是关键的蛋白质生物标志物，通过铁外排的脂质过氧化积累导致铁下垂。通过qPCR、western blot和细胞实验验证，证实了Stat3、Hmox-1和凝固相关基因（Fga、Fgb、Fgg、Serpina1和A2M）的参与。本研究揭示了一种新的FA肝毒性机制，涉及铁下垂和补体和凝血途径，为治疗干预提供了潜力。

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Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis

Formaldehyde (FA) is a well-known environmental toxicant used in various industries, including biomedical, agriculture, and textiles, but poses significant health risks. Despite extensive research, the exact hepatotoxic mechanism of FA remains unclear. This study investigated FA-induced liver toxicity through an integrative analysis of proteomics and metabolomics in rat models, identifying 84 differentially expressed proteins and 66 metabolites. Using xMWAS and Reactome software, the study highlighted ferroptosis as a key pathway in FA-induced liver damage. STAT3/HO-1 were identified as crucial protein biomarkers, leading to ferroptosis via lipid peroxide accumulation through iron efflux. Validation through qPCR, western blot, and cell experiments confirmed the involvement of genes like Stat3, Hmox-1, and coagulation-related genes (Fga, Fgb, Fgg, Serpina1, and A2M). This research reveals a novel FA hepatotoxic mechanism involving ferroptosis and complement and coagulation pathways, offering potential for therapeutic interventions.

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