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

Ruth-Anne RichterDepartments of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
Present address is Reid and Associates, 1630 F Rd, Loxahatchee, FL 33470.

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 DVM, MS
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David E. FreemanDepartments of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Matthew WalligVeterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Ted WhittemVeterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.
Present address is 38 Austral St, Nelson Bay, NSW, Australia.

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Gordon J. BakerDepartment of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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 BVSc, PhD

Abstract

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. (Am J Vet Res 2002;220:934–941)

Abstract

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. (Am J Vet Res 2002;220:934–941)