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Am J Vet Res. 2011 Feb;72(2):226-32. doi: 10.2460/ajvr.72.2.226.

Evaluation of the cyclooxygenase selectivity of robenacoxib and its effect on recovery of ischemia-injured jejunal mucosa in horses.

Author information

  • 1Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. John.F.Marshall@glasgow.ac.uk

Abstract

OBJECTIVE:

To determine the cyclooxygenase (COX) selectivity of robenacoxib and its effect on recovery of jejunal mucosa following ischemic injury in horses.

ANIMALS:

12 healthy horses.

PROCEDURES:

Half the maximal inhibition (EC₅₀) of robenacoxib for COX-1 and COX-2 activity was established in bloods samples from 6 horses via measurement of thromboxane B₂ (TXB₂) and prostaglandin E₂ concentrations, respectively; COX selectivity was subsequently calculated. Six other horses were anesthetized, and ischemia was induced in the jejunum for 2 hours. Control and ischemia-injured mucosa were collected and incubated with Ringer's solution (control treatment), flunixin meglumine (2.7 × 10⁻⁵M), or robenacoxib (2.7 × 10⁻⁵M). Transepithelial electrical resistance and mannitol flux were measured over a 4-hour recovery period. Bathing solution TXB₂ and prostaglandin E metabolite concentrations were measured to assess COX-1 and COX-2 function, respectively.

RESULTS:

The mean ± SD EC₅₀ value of robenacoxib for COX-1 and COX-2 was 11.46 ± 4.46 μM and 0.19 ± 0.07 μM, respectively, resulting in a COX selectivity ratio of 61.01. The transepithelial electrical resistance of ischemia-injured jejunum treated with flunixin meglumine was significantly lower than that of control and robenacoxib-treated tissues. A significant increase in concentrations of prostaglandin E metabolites and TXB₂ was detected in control and robenacoxib-treated tissues but not flunixin meglumine-treated tissues.

CONCLUSIONS AND CLINICAL RELEVANCE:

Robenacoxib selectively inhibited COX-2 and allowed recovery of barrier function in ischemia-injured equine jejunal tissue in vitro.

PMID:
21281197
[PubMed - indexed for MEDLINE]
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