Effect of a zinc l-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo

Tracy L. Hill Department of Clinical Science, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Anthony T. Blikslager Department of Clinical Science, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Abstract

Objective—To examine whether a zinc l-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa.

Sample—Gastric mucosa from 6 healthy dogs.

Procedures—Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc l-carnosine compound, or zinc l-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti–active caspase-3 antibody as an indicator of apoptosis.

Results—Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc l-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc l-carnosine compound did not protect against development of apoptosis.

Conclusions and Clinical Relevance—Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc l-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

Abstract

Objective—To examine whether a zinc l-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa.

Sample—Gastric mucosa from 6 healthy dogs.

Procedures—Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc l-carnosine compound, or zinc l-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti–active caspase-3 antibody as an indicator of apoptosis.

Results—Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc l-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc l-carnosine compound did not protect against development of apoptosis.

Conclusions and Clinical Relevance—Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc l-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

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