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

Objectives-To study the functional and structural responses of the right dorsal colon (RDC) of ponies to phenylbutazone (PBZ) in vitro at a concentration that could be achieved in vivo. Animals-8 adult ponies. Procedure-Short circuit current and conductance were measured in mucosa from the RDC. Tissues incubated with and without HCO₃^- were exposed to PBZ, bumetanide, or indomethacin, Bidirectional Cl^- fluxes were determined. After a baseline flux period, prostaglandin E₂ (PGE₂) was added to the serosal surfaces and a second flux period followed. Light and transmission electron microscopy were performed. Results-Baseline short circuit current was diminished significantly by PBZ and indomethacin, and increased significantly after addictions of PGE₂. After PGE₂ was added, Cl^- secretion increased significantly in tissues in HCO₃^--free solutions and solutions with anti-inflammatory drugs, compared with corresponding baseline measurements and with control tissues exposed to PGE₂. Bumetanide did not affect baseline short circuit current and Cl^- fluxes. The predominant histologic change was apoptosis of surface epithelial cells treated with PBZ and to a lesser extent in those treated with indomethacin. Conclusions and Clinical Relevance-Prostaglandin-induced Cl^- secretion appeared to involve a transporter that might also secrete HCO₃^-. Both PBZ and indomethacin altered ion transport in RDC and caused apoptosis; PBZ can damage mucosa through a mechanism that could be important in vivo. The clinically harmful effect of PBZ on equine RDC in vivo could be mediated through its effects on Cl^- and HCO₃^- secretion.