title: Acetaminophen prevents oxidative burst and delays apoptosis in human neutrophils.
abstract: Acetaminophen is a frequently prescribed over-the-counter drug to reduce fever and pain in the event of inflammatory process. As neutrophils are relevant cells in inflammatory processes, the putative interaction of acetaminophen with these cells, if present, would be of paramount importance. The present study was undertaken to evaluate the effect of acetaminophen in human neutrophils' oxidative burst and lifespan in vitro. The obtained results demonstrate that acetaminophen efficiently modulates neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils, in a concentration-dependent manner, at in vivo relevant concentrations. It was clearly demonstrated that acetaminophen is a strong scavenger of HOCl and H2O2, which probably contributed to the effect observed in neutrophils. Acetaminophen also induced the depletion of glutathione in stimulated neutrophils, suggesting its transformation into a reactive intermediate. Obtained results further revealed that acetaminophen affects programmed cell death of human neutrophils, resulting in a delay of previously stimulated neutrophils-mediated apoptosis. Overall, our data suggested that acetaminophen has considerable potential to be included in anti-inflammatory therapeutic strategies, by preventing biological damage induced by an excessive production of reactive species generated in activated neutrophils and by extending the lifespan of neutrophils, favoring the elimination of pathogens, thus contributing to tissue healing and resolution of inflammation.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Laboratório de Química Aplicada, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. marisafreitas@ff.up.pt
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
authors.forename: Vera M
authors.initials: VM
authors.lastname: Costa
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
authors.forename: Diana
authors.initials: D
authors.lastname: Couto
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002499:Centrifugation, Density Gradient; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018712:Analgesics, Non-Narcotic; D017304:Annexin A5; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D000082:Acetaminophen; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate