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Effects of acetylcysteine and migration of resident eosinophils in an in vitro model of mucosal injury and restitution in equine right dorsal colon

Anna K. RöttingDepartment of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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David E. FreemanDepartment of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Jo Ann C. EurellDepartment of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Peter D. ConstableDepartment of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Matthew WalligDepartment of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

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Abstract

Objectives—To evaluate the in vitro protective effects of acetylcysteine and response of resident mucosal eosinophils in oxidant-induced injury to tissues of right dorsal colon of horses.

Animals—9 adult horses.

Procedure—Gastrointestinal mucosa was damaged in vitro with 3mM hypochlorous acid (HOCl), with and without prior exposure to 6mM acetylcysteine. Control tissues were not exposed to HOCl or acetylcysteine. Control and damaged tissues were incubated in Krebs-Ringer-bicarbonate solution and tissue resistance measured during 240 minutes. Tissue permeability to radiolabeled mannitol was also used to assess mucosal barrier integrity. Tissues were examined by light microscopy before and after HOCl exposure and during and after incubation.

Results—Exposure to HOCl caused tissue damage and decreased tissue resistance. Restitution did occur during the incubation period. Eosinophils were located near the muscularis mucosae in freshly harvested tissues and migrated towards the luminal surface in response to HOCl-induced injury. Compared with tissues treated with HOCl without acetylcysteine, pretreatment with acetylcysteine prevented HOCl-induced tissue damage, changes in resistance, and histologically detectable eosinophil migration. The permeability to mannitol increased to the same extent in tissues treated with HOCl alone or with acetylcysteine and HOCl.

Conclusions and Clinical Relevance—Eosinophils migrated toward the mucosal surface in equine colon in response to oxidant-induced damage in vitro. This novel finding could be relevant to inflammation in equine colon and a pathophysiologic feature of many colonic diseases. Acetylcysteine protected the mucosa against oxidant-induced injury and may be useful as a treatment option for various gastrointestinal tract disorders in horses. (Am J Vet Res 2003;64:1205–1212)

Abstract

Objectives—To evaluate the in vitro protective effects of acetylcysteine and response of resident mucosal eosinophils in oxidant-induced injury to tissues of right dorsal colon of horses.

Animals—9 adult horses.

Procedure—Gastrointestinal mucosa was damaged in vitro with 3mM hypochlorous acid (HOCl), with and without prior exposure to 6mM acetylcysteine. Control tissues were not exposed to HOCl or acetylcysteine. Control and damaged tissues were incubated in Krebs-Ringer-bicarbonate solution and tissue resistance measured during 240 minutes. Tissue permeability to radiolabeled mannitol was also used to assess mucosal barrier integrity. Tissues were examined by light microscopy before and after HOCl exposure and during and after incubation.

Results—Exposure to HOCl caused tissue damage and decreased tissue resistance. Restitution did occur during the incubation period. Eosinophils were located near the muscularis mucosae in freshly harvested tissues and migrated towards the luminal surface in response to HOCl-induced injury. Compared with tissues treated with HOCl without acetylcysteine, pretreatment with acetylcysteine prevented HOCl-induced tissue damage, changes in resistance, and histologically detectable eosinophil migration. The permeability to mannitol increased to the same extent in tissues treated with HOCl alone or with acetylcysteine and HOCl.

Conclusions and Clinical Relevance—Eosinophils migrated toward the mucosal surface in equine colon in response to oxidant-induced damage in vitro. This novel finding could be relevant to inflammation in equine colon and a pathophysiologic feature of many colonic diseases. Acetylcysteine protected the mucosa against oxidant-induced injury and may be useful as a treatment option for various gastrointestinal tract disorders in horses. (Am J Vet Res 2003;64:1205–1212)