In vitro effects of reactive oxygen metabolites, with and without flunixin meglumine, on equine colonic mucosa.
OBJECTIVE
To determine effects of reactive oxygen metabolites (ROMs), with and without flunixin meglumine, on equine right ventral colon (RVC) in vitro.


METHODS
18 healthy horses and ponies.


METHODS
In 3 groups of 6 animals each, short-circuit current and conductance were measured in RVC mucosa in Ussing chambers. The 3 groups received physiologic saline (0.9% NaCl) solution, IV, 10 minutes before euthanasia and tissue incubation in Krebs-Ringer-bicarbonate (KRB) solution; flunixin meglumine (1.1 mg/kg, IV) 10 minutes before euthanasia and tissue incubation in KRB solution; or physiologic saline solution, IV, 10 minutes before euthanasia and incubation in KRB solution with 2.7 x 10(5)M flunixin meglumine. Incubation conditions included control (no addition) and ROM systems, including addition of 1 mM xanthine and 80 mU of xanthine oxidase (to produce the superoxide radical), 1 mM H(2)O(2), and 1 mM H(2)O(2) and 0.5 mM ferrous sulfate (to produce the hydroxyl radical).


RESULTS
All ROMs that were added or generated significantly increased the short-circuit current except in tissues coincubated with flunixin meglumine, and they induced mild epithelial vacuolation and apoptosis, but did not disrupt the epithelium nor change conductance, lactate dehydrogenase release, or [(3)H]mannitol flux.


CONCLUSIONS
Responses to ROMs could be attributed to increased chloride secretion and inhibited neutral NaCl absorption in equine RVC, possibly by stimulating prostaglandin production. The ROMs examined under conditions of this study could play a role in prostaglandin-mediated colonic secretion in horses with enterocolitis without causing direct mucosal injury.
Inoue
Olivia J
OJ
Department of Veterinary Clinical Medicine, College of Veterinary, Medicine, University of Illinois, Urbana, IL 61802, USA.
Freeman
David E
DE
Wallig
Matthew A
MA
Clarkson
Robert B
RB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006736:Horses / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013481:Superoxides; D017665:Hydroxyl Radical; C014558:flunixin meglumine; D006861:Hydrogen Peroxide; D003002:Clonixin