The lipoxygenase-cyclooxygenase inhibitor licofelone prevents thromboxane A2-mediated cardiovascular derangement triggered by the inflammatory peptide fMLP in the rabbit

Serenella Rotondo, Giuseppe Dell'Elba, Stefano Manarini, Chiara Cerletti, Virgilio Evangelista

Research output: Contribution to journalArticlepeer-review

Abstract

Licofelone is an analogue of arachidonic acid that inhibits 5-lipoxygenase (LOX), cyclooxygenase (COX)-1 and COX-2. We investigated the effects of licofelone on cardiovascular derangements and production of thromboxane (Tx)A2 induced by the inflammatory agonist n-formyl-methionyl-leucyl-phenylalanine (fMLP) in the rabbit, in comparison with those of aspirin or rofecoxib, inhibitors of COX-1 and COX-2, respectively. In control rabbits, injection of fMLP (30 nmol/kg) in the jugular vein evokes ischemic electrocardiographic (ECG) changes in the first 1-5 min, i.e. a profound depression of the ST segment and inversion of the T wave. Simultaneously, fMLP induces bradycardia and hypotension and increases TxB2 blood levels. All changes are transient. Licofelone (60 mg/kg/5 days, p.os) prevented fMLP-induced ECG ischemic changes in all treated animals, reverted bradycardia and hypotension, and significantly reduced TxB2. Aspirin (10 mg/kg/5 days, p.os) prevented ischemic ECG alterations in 2 out of 5 treated animals and did not modify either bradycardia or hypotension. One rabbit died two min after fMLP. In 2 rabbits, aspirin reduced TxB2 levels by more than 80% respect to mean control values; the remaining two rabbits produced an amount of TxB2 similar to controls. These two rabbits also showed ischemic ECG changes. Rofecoxib (10 mg/kg/5 days, p.os) did not prevent fMLP-induced ischemic ECG alteration, bradycardia and hypotension, and did not significantly modify the increase of TxB2. These results indicate that the capacity of licofelone to efficiently suppress TxA2 production, is responsible for the protection from the cardiovascular derangement triggered by an inflammatory stimulus.

Original languageEnglish
Pages (from-to)95-101
Number of pages7
JournalEuropean Journal of Pharmacology
Volume546
Issue number1-3
DOIs
Publication statusPublished - Sep 28 2006

Keywords

  • Cardiovascular ischemia
  • COX-1/COX-2-dependent TxA
  • Leukocyte activation
  • Licofelone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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