These authors contributed equally to this work.
The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo
Article first published online: 25 JUL 2011
© 2011 EVJ Ltd
Equine Veterinary Journal
Special Issue: Equine Colic. Guest Editors: T.S. Mair and C.J. Proudman. Publication of this supplement was supported by The Horse Trust
Volume 43, Issue Supplement s39, pages 106–111, August 2011
How to Cite
MARSHALL, J. F., BHATNAGAR, A. S., BOWMAN, S. G., MORRIS, N. N., SKORICH, D. A., REDDING, C. D. and BLIKSLAGER, A. T. (2011), The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo. Equine Veterinary Journal, 43: 106–111. doi: 10.1111/j.2042-3306.2011.00401.x
- Issue published online: 25 JUL 2011
- Article first published online: 25 JUL 2011
- [Paper received for publication 14.01.11; Accepted 16.03.11]
Reasons for performing study: 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 B2 (TXB2) and lipopolysaccharide-stimulated prostaglandin E2 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 3H-mannitol, and bathing solution TXB2 and prostaglandin E metabolites (PGEM) were measured over a 4 h recovery period.
Results: Treatment with AHI-805 had no significant effect on TXB2 production but significantly inhibited production of PGE2 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 TXB2 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.
Potential relevance: The novel compound AHI-805 may not be suitable for the treatment of equine colic associated with ischaemic injury.