Nonsteroidal anti-inflammatory drugs delay
gastric ulcer healing, and the ability of
proton pump inhibitors to counteract this detrimental effect is debated. This study evaluates the effects of
pantoprazole on experimental
gastric ulcer healing in the presence of
indomethacin. Rats with
acetic-acid-induced
gastric ulcers were orally treated for 3 or 7 days with
pantoprazole (15 micromol/kg/day) or
famotidine (20 micromol/kg/day), alone or in combination with
indomethacin (3 micromol/kg/day). Ulcerated tissues were processed to assess
ulcer area,
malondialdehyde,
proliferating cell nuclear antigen (
PCNA) and cleaved
caspase-3. Experiments on pylorus-ligated rats indicated that
pantoprazole and
famotidine were employed at equivalent inhibitory doses on gastric acid secretion (-67.9% and -64.5%, respectively).
Indomethacin delayed
ulcer healing both at days 3 and 7 (+22 and +35 mm(2) vs control
ulcer, respectively). At day 3,
pantoprazole was more effective than
famotidine in promoting
ulcer healing in
indomethacin-treated animals (-53.6 and -31.6 mm(2) vs
indomethacin, respectively).
Malondialdehyde levels and
caspase-3 activation in
ulcers were increased by
indomethacin (+79% and +3.7 folds vs control
ulcer, respectively), and these effects were counteracted by
pantoprazole (-77.9% and -3.5 folds vs
indomethacin, respectively), but not
famotidine. Increments of
ulcer PCNA expression (+2.5 folds vs normal) were enhanced further by
pantoprazole or
famotidine, alone or in combination with
indomethacin (+8.6 and +10.3 folds vs normal, respectively). Similar results were obtained after 7-day treatments of ulcerated animals with test drugs. It is concluded that, along with
acid suppression,
pantoprazole exerts
acid-independent effects on
ulcer healing, which can be ascribed to a decrease in tissue oxidation and apoptosis.