Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows

J Vet Pharmacol Ther. 2013 Apr;36(2):130-9. doi: 10.1111/j.1365-2885.2012.01396.x. Epub 2012 Jun 24.

Abstract

In this study, ex vivo assays were carried out in dairy cows to evaluate the anti-inflammatory effects of two nonsteroidal anti-inflammatory drugs: ketoprofen (KETO) and flunixin meglumine (FM). Twelve healthy Holstein dairy cattle were randomly allocated to two groups (n=6): group 1 received FM and group 2 received KETO at recommended therapeutic dosages. The anti-inflammatory effects of both drugs were determined by measuring the production of coagulation-induced thromboxane B2 (TXB2 ), lipopolysaccharides (LPS) (10 μg/mL)-induced prostaglandin E2 (PGE2 ), and calcium ionophore (60 μm)-induced leukotrien B4 (LTB4 ). Cytokine production was assessed by measuring tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-8 (CXCL8) concentrations after incubation in the presence of 10 μg/mL LPS. The IC50 of FM and KETO was determined in vitro by determining the concentration of TXB2 and PGE2 in the presence of scalar drug concentrations (10(-9) -10(-3) m). Both FM and KETO inhibited the two COX isoforms in vitro, but showed a preference for COX-1. FM and KETO showed similar anti-inflammatory effects in the cow.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Coagulation
  • Cattle / blood
  • Cattle / metabolism*
  • Clonixin / analogs & derivatives*
  • Clonixin / pharmacology
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Gene Expression Regulation / drug effects*
  • Inhibitory Concentration 50
  • Ketoprofen / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • flunixin meglumine
  • Ketoprofen
  • Clonixin