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

The research investigates how nonsteroidal antiinflammatory drugs (NSAIDs) may lessen anion secretion and promote apoptosis in horse colonic mucosa, possibly contributing to a condition known as right dorsal colitis. Key experiments involved measuring the impact of specific drugs on the short-circuit current (Isc) and examining apoptosis levels.

Methodology

• The researchers investigated the effects of two NSAIDs, indomethacin (INDO) and firocoxib (FIR), on the short-circuit current (Isc) in mucosa tissues from the right dorsal colon (RDC) and right ventral colon (RVC) of 20 healthy horses.
• This was done using Ussing chambers and standard electrophysiological techniques.
• Additionally, immunohistochemical methods were used to detect apoptosis using caspase-3 in tissues treated with these NSAIDs and another drug, phenylbutazone (PBZ).
• The same approach was applied to locate the NKCC1 transporter, a protein involved in the regulation of chloride secretion.

Findings

• Isc in RDC and RVC tissues treated with INDO or FIR increased almost three-fold when treated with prostaglandin E2 (PGE2), indicating INDO and FIR could inhibit anion transporters. This increase was inhibited by loop diuretics.
• Although these reactions suggested anion secretion, RDC also showed an Isc response hinting at a unique transporter not present in RVC or NSAID-free solutions.
• FIR, INDO, and PBZ triggered apoptosis in the lower part of crypts in RDC. The research observed significant differences in the apoptotic index between NSAID-treated and control tissues.

Conclusions

• The researchers concluded that the effects of NSAIDs on Isc corresponded with reduced anion secretion, similar to the transport failure responsible for conditions like Cystic Fibrosis in other species.
• Failure of anion secretion could meddle with buffering of acid from intraluminal fermentation, revealing a potential treatment target for right dorsal colitis.