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

Marshall, J.F., Bhatnagar, A.S., Bowman, S.G., Howard, C.M., Morris, N.N., Skorich, D.A., Redding, C.D. and Blikslager, A.T. (2011) Evaluation of the cyclooxygenase selectivity of robenacoxib and its effect on recovery of ischemia-injured jejunal mucosa in horses. American Journal of Veterinary Research, 72(2), pp. 226-232. (doi:10.2460/ajvr.72.2.226)

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Publisher's URL: http://dx.doi.org/10.2460/ajvr.72.2.226

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 B-2 (TXB7) 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 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 mu M and 0.19 +/- 0.07 mu M, 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marshall, Dr John
Authors: Marshall, J.F., Bhatnagar, A.S., Bowman, S.G., Howard, C.M., Morris, N.N., Skorich, D.A., Redding, C.D., and Blikslager, A.T.
College/School:College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:American Journal of Veterinary Research
ISSN:0002-9645

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