Effects of carprofen on the integrity and barrier function of canine colonic mucosa

Catherine A. Briere Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Giselle Hosgood Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Timothy W. Morgan Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Cheryl S. Hedlund Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Merrin Hicks Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Rebecca S. McConnico Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Abstract

Objective—To measure effects of carprofen on conductance and permeability to mannitol and histologic appearance in canine colonic mucosa.

Sample Population—Colonic mucosa from 13 mature mixed-breed dogs.

Procedures—Sections of mucosa from the transverse colon and proximal and distal portions of the descending colon were obtained immediately after dogs were euthanized. Sections were mounted in Ussing chambers. Carprofen (400 μg/mL) was added to the bathing solution for treated sections. Conductance was calculated at 15-minute intervals for 240 minutes. Flux of mannitol was calculated for three 1-hour periods. Histologic examination of sections was performed after experiments concluded. Conductance was graphed against time for each chamber, and area under each curve was calculated. Conductance × time, flux of mannitol, and frequency distribution of histologic findings were analyzed for an effect of region and carprofen.

Results—Carprofen significantly increased mean conductance × time, compared with values for control (untreated) sections for all regions of colon. Carprofen significantly increased mean flux of mannitol from period 1 to period 2 and from period 2 to period 3 for all regions of colon. Carprofen caused a significant proportion of sections to have severe sloughing of cells and erosions involving ≥ 10% of the epithelium, compared with control sections.

Conclusions and Clinical Relevance—Carprofen increased in vitro conductance and permeability to mannitol in canine colonic mucosa. Carprofen resulted in sloughing of cells and erosion of the colonic mucosa. These findings suggested that carprofen can compromise the integrity and barrier function of the colonic mucosa of dogs.

Abstract

Objective—To measure effects of carprofen on conductance and permeability to mannitol and histologic appearance in canine colonic mucosa.

Sample Population—Colonic mucosa from 13 mature mixed-breed dogs.

Procedures—Sections of mucosa from the transverse colon and proximal and distal portions of the descending colon were obtained immediately after dogs were euthanized. Sections were mounted in Ussing chambers. Carprofen (400 μg/mL) was added to the bathing solution for treated sections. Conductance was calculated at 15-minute intervals for 240 minutes. Flux of mannitol was calculated for three 1-hour periods. Histologic examination of sections was performed after experiments concluded. Conductance was graphed against time for each chamber, and area under each curve was calculated. Conductance × time, flux of mannitol, and frequency distribution of histologic findings were analyzed for an effect of region and carprofen.

Results—Carprofen significantly increased mean conductance × time, compared with values for control (untreated) sections for all regions of colon. Carprofen significantly increased mean flux of mannitol from period 1 to period 2 and from period 2 to period 3 for all regions of colon. Carprofen caused a significant proportion of sections to have severe sloughing of cells and erosions involving ≥ 10% of the epithelium, compared with control sections.

Conclusions and Clinical Relevance—Carprofen increased in vitro conductance and permeability to mannitol in canine colonic mucosa. Carprofen resulted in sloughing of cells and erosion of the colonic mucosa. These findings suggested that carprofen can compromise the integrity and barrier function of the colonic mucosa of dogs.

Contributor Notes

Dr. Briere's present address is Boston Veterinary Specialists, 326 Bridge St, Dedham, MA 02026.

Supported by the Charles E. Blass Foundation, Louisiana State University.

The authors thank Catherine Koch and Dr. Kevin Kleinow for technical assistance.

Address correspondence to Dr. Briere.
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