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The cyclooxygenase selectivity and effect of robenacoxib on the recovery of ischemic-injured equine jejunum ex vivo

By J. Marshall, A. Bhatnagar, S. Bowman, C. Howard, N. Morris, D. Skorich, C. Redding and A. Blikslager

Abstract

The objective of this study was to determine the cyclooxygenase (COX) selectivity of robenacoxib and its effect on mucosal recovery following ischemic injury in the horse. Robenacoxib selectivity was determined by assaying its EC50 on COX-1 and COX-2 activity by measuring coagulation-induced thromboxane B2 (TXB2) and lipopolysaccharide-stimulated prostaglandin E2 concentrations respectively. COX selectivity was defined as the EC50 for COX-1 divided by the EC50 for COX-2. Horses (n=6) were anesthetized and jejunum was subjected to 2 hours ischemia. Control and ischemic-injured mucosa was placed in Ussing chambers and treated with Ringer’s solution (control), flunixin meglumine (2.7×10-5M) or robenacoxib (2.7×10-5M). Transepithelial electrical resistance (TER) and 3H-mannitol flux were measured over a 4-hour recovery period. Bathing solution TXB2 and prostaglandin E metabolites (PGEM) were measured to assess COX-1 and COX-2 function respectively. Histological injury grade and percentage epithelial denudation were determined. Results were analyzed using ANOVA, with a statistical significance of p<0.05. The EC50 of robenacoxib for COX-1 and COX-2 was 11.46±4.46μM and 0.19±0.07μM respectively, resulting in a COX selectivity ratio of 61.01. TER of ischemic-injured jejunum treated with flunixin meglumine was significantly lower than that of control and robenacoxib treatment. Ischemic injury significantly increased grade of histological damage, and percentage epithelial denudation. There was no significant effect of treatment. There was a significant increase in PGEM and TXB2 in control and robenacoxib-treated tissues but not flunixin meglumine-treated tissues. Robenacoxib selectively inhibits COX-2 and allows recovery of barrier function in ischemic-injured equine jejunum in-vitro

Topics: RM
Year: 2012
OAI identifier: oai:eprints.gla.ac.uk:46655
Provided by: Enlighten
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