Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia.

The study looks into how the treatment of flunixin meglumine and etodolac impacts the repairing process of damaged equine (horse) intestinal tissue after it has been deprived of oxygen, with findings indicating that these treatments actually slow down the recovery of the intestinal barrier function.

Methodology

• The study involved 24 horses, with the part of the intestine called the jejunum exposed to two hours of ischemia (insufficient blood flow) under anesthesia.
• The horses were then treated with either a saline (0.9% NaCl) solution, flunixin meglumine, or etodolac, at defined dosages and frequency.
• Tissue samples were taken from both damaged (ischemic-injured) and healthy (nonischemic) jejunum right after the ischemia, and then 18 hours after recovery from the ischemia.
• The research team measured the mucosal permeability by noting the transepithelial electric resistance (TER) and the flux of tritium-labelled mannitol across the tissue.
• They calculated the denuded villous surface area (the area of the intestine where the lining has been worn away) and the mean epithelial neutrophil count, which indicates the level of inflammation.
• They also analyzed the presence of cyclooxygenase (COX)-1 and -2 through Western blot analysis. COX is an enzyme involved in inflammation.
• Lastly, the researchers determined the pharmacokinetics of flunixin and etodolac and eicosanoid concentrations – substances related to inflammation and immune response.

Results

• The findings showed that the treatment of flunixin and etodolac caused the ischemic-injured tissue to have significantly lower TER and increased permeability to mannitol, in comparison to saline solution treated horses.
• The research also found no significant difference in epithelial denudation after ischemia and recovery 18 hours later amongst the different treatments.
• Furthermore, both COX-1 and -2 were detected in both the ischemic-induced and non-ischemic tissues, with ischemia causing a significant rise in both COX isoforms.
• Finally, the eicosanoid concentrations were significantly lower in tissues from horses treated with flunixin and etodolac compared to those treated with saline solution.

Conclusion

• The treatment of flunixin and etodolac were found to delay the recovery of the intestinal barrier function in the jejunal mucosa after 18 hours of reviving the blood supply (reperfusion).
• When compared, the tissues from horses treated with saline solution regained the baseline values of TER and permeability to mannitol.