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

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Marshall JF, Bhatnagar AS, Bowman SG, Howard CM, Morris NN, Skorich DA, Redding CD, Blikslager AT

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

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

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21281197 [ View in PubMed
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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 (EC(5)(0)) of robenacoxib for COX-1 and COX-2 activity was established in bloods samples from 6 horses via measurement of thromboxane B(2) (TXB(2)) and prostaglandin E(2) 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 x 10(-)(5)M), or robenacoxib (2.7 x 10(-)(5)M). Transepithelial electrical resistance and mannitol flux were measured over a 4-hour recovery period. Bathing solution TXB(2) and prostaglandin E metabolite concentrations were measured to assess COX-1 and COX-2 function, respectively. RESULTS: The mean +/- SD EC(5)(0) value of robenacoxib for COX-1 and COX-2 was 11.46 +/- 4.46 muM and 0.19 +/- 0.07 muM, 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 TXB(2) 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.

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