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- Author or Editor: Sadasivan Vidyasagar x
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Abstract
OBJECTIVE
To examine bicarbonate (HCO3 −) secretion ex vivo in the equine large colon to determine any differences between the right dorsal colon (RDC) and right ventral colon (RVC). The effect of phenylbutazone (PBZ) on HCO3 − secretion was examined in the RDC.
ANIMALS
14 healthy horses.
PROCEDURES
In anesthetized horses (n = 10), segments of mucosa from RDC and RVC were harvested to measure HCO3 − secretion ex vivo with the pH Stat method. The effect of PBZ on HCO3 − secretion in the RDC was studied in 4 additional horses.
RESULTS
Three distinct mechanisms of HCO3 − secretion previously described in a murine model were confirmed in the equine colon. The RDC had a greater capacity for electrogenic, Cl−-independent HCO3 − secretion than the RVC (P = 0.04). In the RDC, all HCO3 − secretion was decreased by PBZ (P < 0.02) but was not studied in the RVC because of low baseline secretion.
CLINICAL RELEVANCE
Secretion of HCO3 − by the RDC could play a pivotal role in equine colon physiology, because intense microbial fermentation in this site could require HCO3 − secretion to buffer short-chain fatty acids. Inhibition of this secretion by PBZ could interfere with mucosal buffering and predispose to changes associated with right dorsal colitis.
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.
