Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation.
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Lee YS, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA
Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation.
Pain. 2007 Jun;129(3):279-86. Epub 2006 Dec 18.
- PubMed ID
- 17175104 [ View in PubMed]
- Abstract
Acetaminophen is widely used for pain management as an alternative to NSAIDs and selective COX-2 inhibitors, but its action at a molecular level is still unclear. We evaluated acetaminophen's effect on PG release and the expression patterns of genes related to PG production in a clinical model of tissue injury and acute inflammation. Subjects (119 outpatients) received either 1000 mg acetaminophen, 50 mg rofecoxib (a selective COX-2 inhibitor), 30 mg ketorolac (a dual COX-1/COX-2 inhibitor), or placebo before the surgical removal of two impacted mandibular third molars. Microdialysis was used to collect inflammatory transudate from the surgical site for measurement of PGE2 and TXB2 levels at the site of injury. Biopsies were collected to investigate the expression patterns of genes related to PG production at baseline prior to surgery and at 3 or 24 h following surgery. PGE2 release was suppressed by ketorolac, rofecoxib and acetaminophen compared to placebo at 3 h coincident with increased COX-2 gene expression in biopsies collected from the surgical site. TXB2 release was suppressed only by ketorolac. COX-2 gene expression remained elevated at 24 h with continued ketorolac and acetaminophen treatment. COX-1 gene expression was significantly down-regulated at 24 h by ketorolac, rofecoxib and acetaminophen. Acetaminophen suppression of PGE2 without inhibiting TXB2 release, when COX-2 gene expression is up-regulated, suggests that acetaminophen is a selective COX-2 inhibitor in vivo. The up-regulation of COX-2 gene and down-regulation of COX-1 gene expression suggests that acetaminophen may result in changes in COX-derived prostanoids with repeated doses.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Acetaminophen Prostaglandin G/H synthase 2 Protein Humans YesInhibitorDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Acetaminophen Approved PTGS1 5742 downregulated Acetaminophen results in decreased expression of PTGS1 mRNA 9q33.2 Acetaminophen Approved PTGS2 5743 upregulated Acetaminophen results in increased expression of PTGS2 mRNA 1q31.1 Ketorolac Approved PTGS1 5742 downregulated Ketorolac results in decreased expression of PTGS1 mRNA 9q33.2 Ketorolac Approved PTGS2 5743 upregulated Ketorolac results in increased expression of PTGS2 mRNA 1q31.1 Rofecoxib Approved Investigational Withdrawn PTGIS 5740 downregulated rofecoxib results in decreased expression of PTGIS mRNA 20q13.13 Rofecoxib Approved Investigational Withdrawn PTGS1 5742 downregulated rofecoxib results in decreased expression of PTGS1 mRNA 9q33.2