Toxicology and applied pharmacology · 2025
Paracetamol exposure induces rapid alterations in the human plasma proteome.
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Assiri Mohammed A, Almutairi Faris, Alsulais Abdullah, Alhamdan Mohammed F, Almohammed Omar A, Alasmari Fawaz, Albishi Nouf, Aghamdi Ali, AlMuhareb Lamia, AlMotawa Rana, Alrasheed Sara, Aldawsari Feras S, Aloyayd Saud T, Alhejji Abdullah A, Albilali Abdulrazaq, A ElToukhy Riham, Aldrees Ghada A, Bintaleb Doaa A, Benabdelkamel Hicham, Alfadda Assim A, Masood Afshan, Joy Salini Scaria, Alluhaim Wed, Alwhaibi Abdulrahman, Alsanea Sary
Аннотация
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.
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.