Nonsteroidal anti-inflammatory drug administration alters crypt distribution of the peroxisomal marker acyl–coenzyme A oxidase 1 in the equine right dorsal colon

Objective: To characterize and compare the distribution of peroxisomal markers in the right dorsal colon (RDC) and left ventral colon (LVC) of healthy horses and horses treated with NSAIDs. Methods: Archived colonic tissues were evaluated from 10 horses (n = 5/group) administered phenylbutazone (4.4 mg/kg, PO, twice daily for 10 days) or placebo prior to euthanasia. Samples from the RDC and LVC were analyzed using immunofluorescence to assess peroxisomal biogenesis factor 14 (PEX14) and acyl-coenzyme A oxidase 1 (ACOX1) distribution. Marker abundance was quantified within colonic crypts and compared by region, crypt axis (tip, mid, base), and treatment group. Results: In control horses, no differences in PEX14 or ACOX1 distribution were detected between the RDC and LVC. The ACOX1 fluorescence area per cell was greater at the crypt tip than the base in both regions, whereas PEX14 distribution did not differ along the crypt axis. Nonsteroidal anti-inflammatory drug administration was not associated with differences in PEX14 distribution in either region. In NSAID-treated horses, ACOX1 area per cell at the crypt tip was greater in the RDC than the LVC (mean difference, 1.66 μ2/nuclei; 95% CI, 0.35 to 2.97). Conclusions: Peroxisomal marker distribution did not differ between the RDC and LVC in healthy horses. In NSAID-treated horses, ACOX1 per cell was greater at the crypt tip in the RDC, suggesting a region-specific response to NSAIDs. Clinical Relevance: Region-specific differences in peroxisomal-associated pathways may contribute to the susceptibility of the RDC to NSAID-induced injury and warrant further investigation into underlying mechanisms and prevention strategies.