Nonsteroidal antiinflammatory drugs reduce anion secretion and increase apoptosis in equine colonic mucosa ex vivo

Abstract

Abstract OBJECTIVE Right dorsal colitis causes chronic colic associated with long-term treatment with nonsteroidal antiinflammatory drugs (NSAIDs). This study was designed to determine if NSAIDs could inhibit anion transporters that protect against intestinal mucosal injury in other species. ANIMALS 20 healthy horses. METHODS The effects of indomethacin (INDO) and firocoxib (FIR), on short-circuit current (Isc) in mucosa from the right dorsal colon (RDC) and right ventral colon (RVC) were measured in Ussing chambers by standard electrophysiological techniques. Immunohistochemical methods were used to detect apoptosis (caspase-3) with these NSAIDs and phenylbutazone (PBZ) and to locate the NKCC1 transporter. RESULTS The Isc in RDC and RVC incubated with INDO or FIR was increased almost 3-fold (P < .0001) by prostaglandin E2 (PGE2) through a system inhibited by loop diuretics (P < .0001). Although these findings and anion replacement studies were consistent with anion secretion, the RDC also displayed an Isc response suggestive of a unique transporter apparently absent in RVC or NSAID-free solutions. In RDC, FIR, INDO, and PBZ induced apoptosis in the lower half of crypts. However, significant differences in apoptotic index were recorded in the RDC between NSAID-treated and control tissues (no NSAID). CLINICAL RELEVANCE The effects of NSAIDs on Isc were consistent with reduced anion secretion, which could represent the pharmacological equivalent of the transport failure responsible for Cystic Fibrosis (CF) in other species. Failure of anion secretion could interfere with buffering acid from intraluminal fermentation, which could suggest a treatment target for right dorsal colitis.