Carprofen compromises the integrity and barrier function of the colonic mucosa of the dog

Abstract

Effects of carprofen on colon of dog have not been investigated. Objectives 1) Measure conductance and permeability to mannitol of transverse, proximal descending and distal descending colonic mucosa of dog. 2) Measure conductance and permeability to mannitol of colonic mucosa of dog in presence of carprofen. Design In vitro experimental - nested, randomized block design Animals Colonic mucosa from 6 (objective 1) and 7 (objective 2) mature mixed-breed dogs. Methods Objective 1) Control - Three sections of mucosa from each region of colon were mounted in Ussing chamber units. Conductance was calculated every 15 min for 240 min. Flux of mannitol was calculated for three periods of one hour. Objective 2) Carprofen - Methods based on results for objective 1. Sections of mucosa were prepared as in objective 1. Carprofen (400μg/ml) was added to bathing solution. Data for conductance and flux of mannitol was obtained as in objective 1. Histologic examination of all sections was performed after experiment. For both objectives, conductance was graphed against time for each chamber and area under each curve calculated. Conductance*time, flux of mannitol and frequency distribution of histologic categories were used for analysis. Results Objective 1) Mean +/- SEM conductance*time transverse colonic mucosa was higher than proximal and distal descending. Mean +/- SEM flux of mannitol increased from period 1 to period 3 for transverse colonic mucosa. Objective 2) Data from objective 1 was used as control for objective 2. Mean +/- SEM conductance*time carprofen group was higher than control group for all regions of colon. For carprofen group, mean +/- SEM flux of mannitol increased from period 1 to period 2 and from period 2 to period 3 for all regions of colon. There was higher proportion of sections with severe sloughing of cells and erosions involving more than 10% of epithelium in carprofen group compared to control. Conclusion Carprofen increases in vitro conductance and permeability to mannitol and causes sloughing of cells and erosions of colonic mucosa of dog which suggests compromise of integrity and loss of barrier function.