title: Evaluation of the cyclooxygenase selectivity of robenacoxib and its effect on recovery of ischemia-injured jejunal mucosa in horses.
abstract: OBJECTIVE
  To determine the cyclooxygenase (COX) selectivity of robenacoxib and its effect on recovery of jejunal mucosa following ischemic injury in horses.
  
  
  METHODS
  12 healthy horses.
  
  
  METHODS
  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
  Robenacoxib selectively inhibited COX-2 and allowed recovery of barrier function in ischemia-injured equine jejunal tissue in vitro.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. John.F.Marshall@glasgow.ac.uk
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
authors.forename: Adria S
authors.initials: AS
authors.lastname: Bhatnagar
authors.forename: Susan G
authors.initials: SG
authors.lastname: Bowman
authors.forename: Christina M
authors.initials: CM
authors.lastname: Howard
authors.forename: Natalie N
authors.initials: NN
authors.lastname: Morris
authors.forename: Dinah A
authors.initials: DA
authors.lastname: Skorich
authors.forename: Caitlyn D
authors.initials: CD
authors.lastname: Redding
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Blikslager
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007410:Intestinal Diseases / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D007511:Ischemia / Q000473:pathology / Q000662:veterinary*; D007583:Jejunum / Q000473:pathology*; D010648:Phenylacetates / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D016861:Cyclooxygenase Inhibitors; D010648:Phenylacetates; D004159:Diphenylamine; D051545:Cyclooxygenase 1; C551524:robenacoxib