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Am J Vet Res. 2003 Feb;64(2):211-5.

Evaluation of the ability of carprofen and flunixin meglumine to inhibit activation of nuclear factor kappa B.

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1
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Rd, Cambridge, UK CB3 OES.

Abstract

OBJECTIVE:

To determine whether the nonsteroidal anti-inflammatory drugs (NSAIDs) carprofen, flunixin meglumine, and phenylbutazone have cyclooxygenase (COX)-independent effects that specifically inhibit activation of the proinflammatory transcription factor nuclear factor kappa B (NfkappaB).

STUDY POPULATION:

Purified ovine COX-1 and -2 and cultures of RAW 264.7 murine macrophages.

PROCEDURE:

The COX-1 and -2 inhibitory effects of the NSAIDs were tested in assays that used purified ovine COX-1 and -2. Prostaglandin production was analyzed by use of a radioimmunoassay. Inhibitory effects of these drugs on lipopolysaccharide (LPS)-induction of inducible nitric oxide synthase (iNOS) and LPS-stimulated translocation of NficB were determined by use of RAW 264.7 murine macrophages.

RESULTS:

Flunixin meglumine and phenylbutazone were selective inhibitors of COX-1. Carprofen and flunixin meglumine, but not phenylbutazone, inhibited LPS-induction of iNOS. Carprofen and, to a lesser degree, flunixin meglumine had inhibitory effects on NFkappaB activation.

CONCLUSIONS AND CLINICAL RELEVANCE:

The ability of drugs such as carprofen and flunixin meglumine to inhibit activation of NfkappaB-dependent genes such as iNOS, in addition to their effects on COX, suggests an additional mechanism for their anti-inflammatory effects and may explain the ability of flunixin meglumine to be an effective inhibitor of the effects of endotoxin in horses with endotoxemia.

PMID:
12602591
[Indexed for MEDLINE]
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