The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischemic-injured equine jejunum ex vivo

Marshall, J., Bhatnagar, A., Bowman, S., Morris, N., Skorich, D. and Blikslager, A. (2012) The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischemic-injured equine jejunum ex vivo. Equine Veterinary Journal, pp. 106-111. (doi:10.1111/j.2042-3306.2011.00401.x)

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Abstract

Reasons for performing study: Flunixin meglumine continues to be used for treatment of equine colic despite evidence of inhibited recovery of mucosal barrier function following small intestinal ischemic injury. This study aimed to characterize 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 ischemic injury. Methods: The 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 respectively in equine whole blood. Horses (n=6) were anesthetized and jejunum was subjected to ischemia for 2 hours. Control and ischemic-injured mucosa was placed in Ussing chambers and treated with Ringer’s solution containing control treatment (DMSO), flunixin meglumine (2.7×10-5M), or AHI-805 (2.7×10-5M). Trans-epithelial electrical resistance (TER) and mucosal-to-serosal flux of 3H-mannitol were measured over a 4-hour recovery period. Bathing solution TXB2 and prostaglandin E metabolites (PGEM) were measured by enzyme immunoassay (EIA) to assess COX-1 and COX-2 function respectively. Results: Treatment with AHI-805 had no significant effect on coagulation induced TXB2 production but significantly inhibited production of LPS-induced PGE2 at a concentration of 1µM or greater. TER of flunixin or AHI-805 treated ischemic-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 ischemic injury but not treatment. There was a significant increase in PGEM and TXB2 in control tissues over the 240 minute recovery period, but not in flunixin or AHI-805 treated tissues. Conclusions: Flunixin meglumine and AHI-805 inhibit recovery of barrier function in ischemic-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 ischemic injury.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marshall, Dr John
Authors: Marshall, J., Bhatnagar, A., Bowman, S., Morris, N., Skorich, D., and Blikslager, A.
Subjects:R Medicine > RS Pharmacy and materia medica
R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Equine Veterinary Journal
ISSN:0425-1644

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