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

This research investigates the impact of a new anti-inflammatory compound (AHI-805) on certain enzymes and the recovery of a specific part of a horse’s intestine following ischemic injury, and concludes that the compound may not be suitable for treating horse colic related to this type of injury.

Background and Objective

• The study’s main focus is on an alternative treatment for abdominal pain in horses. Specifically, the researchers were investigating a new compound called AHI-805. Its potential effects on cyclooxygenase enzymes and the recovery of the mucosal barrier function following ischemic injury were central to the study.
• Flunixin meglumine, commonly used for treating equine colic (a severe digestive disorder in horses), has been found to potentially inhibit the recovery of intestinal function following an ischemic injury. An ischemic injury refers to damage caused by limited blood supply to an area of the body, in this case, the small intestine.
• The objective was to ascertain if AHI-805 could serve as an effective substitute without the potential downsides of flunixin meglumine.

Methods

• The researchers first determined the effect of AHI-805 on COX-1 and COX-2 (Cyclooxygenase enzymes involved in inflammation) activity by performing an in vitro measurement of coagulation-induced thromboxane B(2) (TXB(2)) and lipopolysaccharide-stimulated prostaglandin E(2) concentrations in equine whole blood.
• Equine jejunum (a part of the small intestine in horses) was subjected to ischemia for 2 hours. After this, affected tissues were placed in Ussing chambers and treated with a control treatment, flunixin meglumine, or AHI-805.
• Several metrics were then recorded over a 4-hour recovery period. These included Transepithelial electrical resistance (TER, indicating barrier function), mucosal-to-serosal flux of H-mannitol (a measure of permeability), and bathing solution TXB(2) and prostaglandin E metabolites (PGEM, markers of inflammation).

Results

• AHI-805 treatment did not significantly alter TXB(2) production but significantly blocked the production of PGE(2) at concentrations of 1 µmol/l or more.
• The study showed that treatment with either flunixin meglumine or AHI-805 led to significantly lower TER (indicating worse barrier function) in ischemia-injured jejunum than the control treatment.
• Ischemic injury alone significantly increased the mannitol flux and the degree of histological damage.
• Neither flunixin meglumine nor AHI-805 treatment led to increased PGEM or TXB(2) in the tissues over the recovery period.

Conclusions

• The research concluded that both flunixin meglumine and AHI-805 inhibit the recovery of barrier function in the ischemia-injured equine jejunum. This inhibition was ascribed to the treatment’s effect on the COX enzymes.
• Based on these results, the study concluded that AHI-805 may not be suitable for treating equine colic associated with ischemic injury. This indicates a need for further research to develop more effective treatments for this condition in horses.