title: In vitro effect of carprofen and meloxicam on the conductance and permeability to mannitol and the histologic appearance of the gastric mucosa of dogs.
abstract: OBJECTIVE
  To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa.
  
  
  METHODS
  Gastric mucosa from 6 mature mixed-breed dogs.
  
  
  METHODS
  Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400μg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80μg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects.
  
  
  RESULTS
  For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections.
  
  
  CONCLUSIONS
  In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 μg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.
authors: Departments of Veterinary Clinical Sciences, School of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. mh@petemergency.com.au
authors: Merrin A
authors: MA
authors: Hicks
authors: Giselle L
authors: GL
authors: Hosgood
authors: Timothy W
authors: TW
authors: Morgan
authors: Catherine A
authors: CA
authors: Briere
authors: Rebecca S
authors: RS
authors: McConnico
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D004234:Diuretics, Osmotic / Q000494:pharmacology*; D004285:Dogs / Q000033:anatomy & histology / Q000502:physiology*; D005753:Gastric Mucosa / Q000033:anatomy & histology / Q000502:physiology*; D008353:Mannitol / Q000494:pharmacology; D000077239:Meloxicam; D010539:Permeability; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D004234:Diuretics, Osmotic; D013843:Thiazines; D013844:Thiazoles; D008353:Mannitol; C007005:carprofen; D000077239:Meloxicam