Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine

Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
James Coulson, John P Thompson

Abstract

The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro. HMC-1 and human PBMCs were incubated in the presence of increasing concentrations of NAC +/- paracetamol. Cell viability was determined by the Trypan Blue Assay, and histamine secretion was measured by ELISA. NAC was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC-1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and 2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell types was reduced by co-incubation with 2.5 mg/mL of paracetamol. Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro. This may explain the clinical observation of a lower incidence of adverse reactions to NAC in vivo when higher concentrations of paracetamol are present than when paracetamol concentrations are low. Paracetamol (acetaminophen) attenuates in vitro mast ce...Continue Reading

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Citations

Feb 15, 2013·Journal of Anesthesia·Norma J Klein, Shad Misseldine
Jul 19, 2013·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·James Michael Coulson, John Paul Thompson
Sep 24, 2013·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Rana Biary, Robert S Hoffman
Sep 25, 2012·Critical Care Clinics·Michael J Hodgman, Alexander R Garrard
Dec 1, 2012·Therapeutic Advances in Drug Safety·W Stephen Waring
Jun 16, 2012·Expert Review of Clinical Pharmacology·W Stephen Waring
Oct 12, 2019·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Alaa DaoudTonny Studsgaard Petersen
Aug 26, 2016·British Journal of Clinical Pharmacology·George P BaileyPaul I Dargan
Jul 15, 2015·The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG·Kathryn A PauleyD Adam Algren

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