Paracetamol suppresses neutrophilic oxygen radicals through competitive inhibition and scavenging

Chem Biol Interact. 2024 Dec 1:404:111283. doi: 10.1016/j.cbi.2024.111283. Epub 2024 Oct 19.

Abstract

Neutrophils, pivotal cells of innate and adaptive immune responses, employ reactive oxygen species (ROS) to combat pathogens and control gene expression. Paracetamol (acetaminophen) is widely used as an analgesic and antipyretic medication, yet its precise mechanisms of action are not yet fully understood. Here, we investigate the impact of both ingested and in-vitro paracetamol on neutrophil ROS activity, using flow cytometry and antioxidant assays. Our studies reveal that paracetamol significantly suppresses ROS activity ex-vivo in the short term. Additionally, both paracetamol and its metabolite N-acetyl-p-benzoquinone imine exhibited direct in vitro antioxidant effects, and paracetamol suppressed neutrophil extracellular trap formation ex vivo. These findings suggest a connection between paracetamol use and altered neutrophil responses, with potential implications for use in some patient groups, such as immunocompromised individuals. Further investigation into paracetamol's effects on neutrophil antimicrobial functions is warranted to elucidate possible risks, particularly when taken frequently or in conjunction with other treatments such as vaccinations.

Keywords: Acetaminophen; Inflammation; NETs; Neutrophils; Oxidative burst; Paracetamol.

MeSH terms

  • Acetaminophen* / pharmacology
  • Antioxidants / pharmacology
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology
  • Extracellular Traps* / drug effects
  • Extracellular Traps* / metabolism
  • Free Radical Scavengers / pharmacology
  • Humans
  • Imines / chemistry
  • Imines / pharmacology
  • Neutrophils* / drug effects
  • Neutrophils* / metabolism
  • Reactive Oxygen Species* / metabolism

Substances

  • Acetaminophen
  • Reactive Oxygen Species
  • Benzoquinones
  • N-acetyl-4-benzoquinoneimine
  • Antioxidants
  • Free Radical Scavengers
  • Imines