title: Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum.
abstract: BACKGROUND
  Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)-2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti-inflammatory drugs in colic patients.
  
  
  OBJECTIVE
  To compare the effects of deracoxib, a highly selective canine COX-2 inhibitor, with flunixin on in vitro recovery of ischaemic-injured equine jejunum.
  
  
  METHODS
  Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 240 mins. Transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol were monitored as indices of barrier function in the presence of flunixin or deracoxib.
  
  
  RESULTS
  The TER of ischaemic-injured tissue recovered significantly over 240 mins in the presence of no treatment, but not in the presence of flunixin or deracoxib. In addition, flunixin-treated ischaemic jejunum was significantly more permeable to mannitol when compared with untreated tissue by the end of the recovery period, whereas deracoxib treatment did not increase permeability. Addition of the PGE1 analogue misoprostol to flunixin-treated tissue restored recovery of TER.
  
  
  CONCLUSIONS
  Treatment of horses with ischaemic jejunal disease with flunixin may result in a prolonged permeability defect in recovering mucosa. Addition of misoprostol or replacement of flunixin with deracoxib may ameliorate effects of COX inhibitors on recovering mucosa.
authors.affiliation: Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27606, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Tomlinson
authors.forename: A T
authors.initials: AT
authors.lastname: Blikslager
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001692:Biological Transport; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017097:Electric Impedance; D006652:Histological Techniques; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy / Q000662:veterinary*; D007583:Jejunum / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D016595:Misoprostol / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D015424:Reperfusion / Q000662:veterinary; D013449:Sulfonamides / Q000494:pharmacology*; D014316:Tritium; D000096926:Benzenesulfonamides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003002:Clonixin; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008353:Mannitol; D016595:Misoprostol; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D013449:Sulfonamides; D014316:Tritium; C014557:flunixin; C471996:deracoxib; D000096926:Benzenesulfonamides