Effects of the novel anti‐inflammatory drugs robenacoxib and AHI‐805 on recovery of ischemic injured equine jejunum ex vivo

Abstract

Flunixin is an NSAID administered to horses to ameliorate shock, but which inhibits recovery of barrier function in ischemic‐injured intestine. We examined the effect of robenacoxib, a COX‐2 inhibitor, and AHI‐805, an aza‐thia‐benzoazulene derivative, on recovery of mucosal barrier function. Jejunum was subjected to ischemia for 2 hours in 6 horses. Control and ischemic‐injured mucosa was treated with Ringer's alone (control) or containing 0.27μM flunixin, robenacoxib, or AHI‐805 in Ussing chambers. Trans‐epithelial electrical resistance (TER) and mucosal‐to‐serosal flux of 3H‐mannitol were measured over a 4‐hour period. TXB2 and PGEM in the serosal bathing solution were measured to assess COX‐1 and COX‐2 function. Expression of COX‐1 and ‐2 was determined by immunoblot and histology was performed. Ischemic injury significantly increased 3H‐mannitol flux, epithelial denudation, and COX‐2 expression (P<0.05). TER of ischemic‐injured tissue treated with flunixin or AHI‐805 was significantly lower than control over the recovery period (P<0.05). Robenacoxib did not inhibit recovery of TER. PGEM and TXB2 were significantly decreased by flunixin and AHI‐805 when compared to Ringer's alone or robenacoxib. Robenacoxib permits recovery of ischemic‐injured jejunum judging by indices of barrier function, and this is linked to its ability to allow enhanced PG production.