Paracetamol exposure induces rapid alterations in the human plasma proteome

IF 3.4 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-08-09 DOI:10.1016/j.taap.2025.117501

Mohammed A. Assiri , Faris Almutairi , Abdullah Alsulais , Mohammed F. Alhamdan , Omar A. Almohammed , Fawaz Alasmari , Nouf Albishi , Ali Aghamdi , Lamia AlMuhareb , Rana AlMotawa , Sara Alrasheed , Feras S. Aldawsari , Saud T. Aloyayd , Abdullah A. Alhejji , Abdulrazaq Albilali , Riham A.ElToukhy , Ghada A. Aldrees , Doaa A. Bintaleb , Hicham Benabdelkamel , Assim A. Alfadda , Sary Alsanea

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Abstract

Background

Paracetamol is a widely used analgesic and antipyretic, yet its effect on human plasma proteome remains poorly characterized. This study aims to evaluate the impact of a single therapeutic dose of paracetamol on the plasma proteome, potentially providing insights into its pharmacological and toxicological pathways.

Methods

We conducted a cross-sectional study with 28 age-matched fasting subjects (14 controls and 14 treated with paracetamol). Anthropometric measurements and laboratory parameters were assessed, and blood samples were collected. An untargeted label-free LC-MS/MS approach, bioinformatics, and network pathway analysis were employed to examine changes in the proteomic profile.

Results

Proteomic analyses revealed significant differences in plasma protein abundance between the groups. A total of 78 dysregulated proteins were identified, with 23 upregulated and 55 downregulated in the paracetamol group. Transthyretin and vascular cell adhesion protein 1 were upregulated, while doublecortin domain-containing protein 1 and alpha-1-acid glycoprotein 1 were downregulated. These proteins were associated with key pathways, including ligand binding, Fc gamma receptor-dependent phagocytosis, and IL-12 signaling.

Conclusion

This proteomic analysis lays the groundwork for further studies to elucidate the mechanisms underlying paracetamol's therapeutic and toxicological effects by highlighting significant dysregulated proteins and related pathways.

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扑热息痛暴露会引起人类血浆蛋白质组的快速改变

背景：扑热息痛是一种广泛使用的镇痛和解热药物，但其对人类血浆蛋白质组的影响尚不清楚。本研究旨在评估单次治疗剂量扑热息痛对血浆蛋白质组的影响，为其药理学和毒理学途径提供潜在的见解。方法我们对28名年龄匹配的空腹受试者进行了横断面研究（14名对照，14名服用扑热息痛）。评估人体测量值和实验室参数，并采集血样。采用非靶向无标记LC-MS/MS方法、生物信息学和网络通路分析来检测蛋白质组学谱的变化。结果蛋白质组学分析显示各组血浆蛋白丰度存在显著差异。共鉴定出78个失调蛋白，在扑热息痛组中有23个上调，55个下调。转甲状腺素和血管细胞粘附蛋白1上调，双皮质素结构域蛋白1和α -1-酸性糖蛋白1下调。这些蛋白与关键途径相关，包括配体结合、Fc受体依赖性吞噬和IL-12信号传导。结论该蛋白质组学分析为进一步阐明扑热息痛的治疗和毒理学作用机制奠定了基础，揭示了重要的异常蛋白和相关途径。

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.