Effects of flunixin meglumine on short circuit current in equine colonic mucosa in vitro.

The article details a comprehensive experimental investigation into the effects of flunixin meglumine, a non-steroidal anti-inflammatory drug, on short circuit current (Isc) in the right ventral colon of horses and ponies, exploring the mechanisms behind its potential alteration of colonic prostaglandins.

Experimental Methods

• The research involved multiple experiments on healthy horses and ponies, employing Ussing chambers to measure Isc in the mucosa from the right ventral colon.
• The first experiment exposed the equine colonic mucosa samples to an array of solutions including a control solution devoid of additions, flunixin meglumine at a concentration of 4 micrograms/ml, indomethacin at a different concentration, and finally a combination of flunixin meglumine and prostaglandin E2.
• In the second experiment, different incubation conditions were analysed, such as flunixin meglumine in a plain Krebs-Ringer bicarbonate (KRB) solution and in a chloride-free buffer solution, alongside investigating the effects of substituting chloride with isethionate.
• The third experiment involved treatment of animal groups with flunixin meglumine before euthanasia, or through the addition of the drug to all tissue preparation and incubation solutions, with a control group for comparison.

Research Findings

• Both flunixin meglumine and indomethacin significantly reduced Isc to about a third of the control current, indicating their substantial influence on the colonic function in horses and ponies. Conversely, these reductions were reversed to levels close to control when both substances were used in conjunction with prostaglandin E2.
• On a standalone basis, prostaglandin E2 displayed no significant effects on Isc.
• When chloride was substituted with isethionate, flunixin meglumine exhibited no discernible influence on Isc. This suggests that the drug’s effects are connected with chloride-dependent mechanisms, possibly related to chloride secretion.
• Flunixin meglumine reduced Isc when given prior to euthanasia or included at a concentration level in all tissue preparation and incubation solutions.

Conclusion

Flunixin meglumine, whether administered intravenously or added to bathing solutions, was found to reduce Isc in the right ventral colon of horses, with the reduction mechanism seemingly involving prostaglandin-mediated chloride secretions. These insights imply that flunixin meglumine, when given intravenously at approved dosages to horses, could potentially alter the actions of colonic prostaglandins.