JBP485 treatment ameliorated indomethacin-induced enteropathy characterized by severe histopathological changes and a large number of TUNEL-positive cells in rat intestinal epithelium, elevated levels of MDA, MPO, TNF-α, IL-6, IL-1β and increased expression of COX-2, and reduced levels of SOD, GSH, CAT, HDL-c, PGE2, expression of COX-1 and Bcl-2/Bax ratio in rat intestinal tissues.
While selective COX-2 inhibitors are associated with fewer gastro-duodenal complications relative to non-selective NSAIDs, their comparative benefit in protecting against small bowel enteropathy remains unclear.
COX-2 mRNA was upregulated > 2 fold in intestinal mucosa with enteropathy and dose-dependent mitochondrial oxidative damage was apparent in gastric and intestinal mucosa.