In vitro anion transport alterations and apoptosis induced by phenylbutazone in the right dorsal colon of ponies.

The research investigated the effects of the drug phenylbutazone on the right dorsal colon of ponies, specifically looking at changes in anion transport and increase in cell death (apoptosis). The study found that the drug altered ion transport and caused cell death, potentially contributing to damage in the colon.

Study methodology

• The study subjected the right dorsal colon (RDC) of 8 adult ponies to different concentrations of phenylbutazone – a concentration based on what could be achievable in a live pony.
• Using different tests, the researchers measured changes in short circuit current and conductance in the colon’s mucosa. The tissues were prepared in conditions using a molecule named HCO3-, and then exposed to phenylbutazone, bumetanide, or indomethacin.
• The researchers also investigated the move of chloride ions (Cl-) in both directions across the colon tissue.
• The tissue was then exposed to another substance, prostaglandin E2 (PGE2), and measurements were taken after the exposure.
• Finally, the scientists used light and transmission electron microscopy to examine microscopic changes in the tissue structure.

Main findings

• The introduction of phenylbutazone and indomethacin significantly reduced the baseline short circuit current in the tissues.
• The presence of PGE2 led to an increase in the Cl- secretion, particularly in tissues in HCO3-free solutions and solutions with anti-inflammatory drugs, compared to baseline and control tissues.
• In contrast, the other tested substance, bumetanide, did not cause significant changes in baseline short circuit current and Cl- fluxes.
• Microscopic examinations found a profound increase in apoptosis (cell death) in cells treated with phenylbutazone. Apoptosis also occurred, although to a lesser extent, in tissues treated with indomethacin.

Conclusions and implications

• The Cl- secretion induced by prostaglandin seemed to involve a transporter mechanism that might also handle HCO3- secretion.
• Both phenylbutazone and indomethacin affected ion transport and caused apoptosis in the right dorsal column, with phenylbutazone having more significant effects.
• These findings suggest that phenylbutazone might damage the mucosa tissue, indicating a possible mechanism of damage that could be significant in living ponies.
• Given the study results, it’s proposed the harmful effect of phenylbutazone on the right dorsal column could be primarily through its impact on Cl- and HCO3- secretion.