title: The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo.
abstract: BACKGROUND
  Flunixin meglumine is used for treatment of equine colic despite evidence of inhibited recovery of mucosal barrier function following small intestinal ischaemic injury. This study aimed to characterise an alternative treatment (AHI-805) for abdominal pain in the horse.
  
  
  OBJECTIVE
  To determine the effect of AHI-805, an aza-thia-benzoazulene derivative, on the cyclooxygenase enzymes and the recovery of mucosal barrier function following ischaemic injury.
  
  
  METHODS
  Effect of AHI-805 on in vitro COX-1 and COX-2 activity was determined by measuring coagulation-induced thromboxane B(2) (TXB(2)) and lipopolysaccharide-stimulated prostaglandin E(2) concentrations in equine whole blood. Horses (n = 6) were anaesthetised and jejunum subjected to ischaemia for 2 h. Control and ischaemia injured mucosa was placed in Ussing chambers and treated with Ringer's solution containing control treatment (DMSO), flunixin meglumine (27 µmol/l), or AHI-805 (27 µmol/l). Transepithelial electrical resistance (TER), mucosal-to-serosal flux of (3) H-mannitol, and bathing solution TXB(2) and prostaglandin E metabolites (PGEM) were measured over a 4 h recovery period.
  
  
  RESULTS
  Treatment with AHI-805 had no significant effect on TXB(2) production but significantly inhibited production of PGE(2) at a concentration of 1 µmol/l or greater. TER of flunixin or AHI-805 treated ischaemia-injured jejunum was significantly lower than control treated injured tissue over the recovery period. Mannitol flux and grade of histological damage were significantly increased by ischaemic injury only. There was a significant increase in PGEM and TXB(2) in control tissues over the 240 min recovery period, but not in flunixin or AHI-805 treated tissues.
  
  
  CONCLUSIONS
  Flunixin meglumine and AHI-805 inhibit recovery of barrier function in ischaemic-injured equine jejunum in vitro through inhibition of the COX enzymes.
  
  
  CONCLUSIONS
  The novel compound AHI-805 may not be suitable for the treatment of equine colic associated with ischaemic injury.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, NC, USA. John.F.Marshall@glasgow.ac.uk
authors.forename: J F
authors.initials: JF
authors.lastname: Marshall
authors.forename: A S
authors.initials: AS
authors.lastname: Bhatnagar
authors.forename: S G
authors.initials: SG
authors.lastname: Bowman
authors.forename: N N
authors.initials: NN
authors.lastname: Morris
authors.forename: D A
authors.initials: DA
authors.lastname: Skorich
authors.forename: C D
authors.initials: CD
authors.lastname: Redding
authors.forename: A T
authors.initials: AT
authors.lastname: Blikslager
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D052176:Azulenes / Q000494:pharmacology*; D002102:Cadaver; D003002:Clonixin / Q000031:analogs & derivatives; D051545:Cyclooxygenase 1 / Q000097:blood / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000097:blood / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017097:Electric Impedance; D006736:Horses / Q000097:blood*; D007413:Intestinal Mucosa / Q000187:drug effects; D007511:Ischemia / Q000150:complications*; D007583:Jejunum / Q000201:enzymology* / Q000293:injuries*
chemical_list: C570524:AHI-805; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052176:Azulenes; D016861:Cyclooxygenase Inhibitors; C014558:flunixin meglumine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003002:Clonixin