Effect of naproxen on the hamster gastric antrum: ulceration, adaptation and efficacy of anti-ulcer drugs.
BACKGROUND
Various animal models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulceration exist. These models have limitations, which make them less relevant to the human situation.


OBJECTIVE
: To develop a more simple and more relevant model of NSAID-induced gastric ulceration and adaptation.


METHODS
Gastric ulceration was evaluated following the orogastric administration of naproxen (80 mg/kg b.d.) to hamsters. The effects of misoprostol and famotidine on gastric acid secretion and ulceration were also determined. Gastric adaptation was evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemistry, in hamsters given naproxen for 3 weeks. Antral resistance to acute injury by NSAIDs and ethanol was also determined in these animals.


RESULTS
Naproxen caused primarily gastric antral ulceration, which decreased from day 3 to day 21. This gastric adaptation was accompanied by an increase in PCNA positive cells, particularly on days 7 and 14. The adapted gastric antral mucosa was resistant to acute damage by various agents. Misoprostol (1 or 100 microg/kg) prevented antral ulceration, without affecting gastric acid secretion. Despite decreasing acid output by> 90%, famotidine (30 mg/kg) failed to prevent ulceration.


CONCLUSIONS
The administration of naproxen (80 mg/kg b.d.) to hamsters is a simple, reliable and relevant method for evaluating NSAID-induced gastric antral ulceration and adaptation.
Fitzpatrick
L R
LR
Gastrointestinal Inflammation Department, Maryland Research Laboratories, Otsuka America Pharmaceutical Inc., Rockville, Maryland 20850, USA. leof@mrl.oapi.com
Sakurai
K
K
Le
T
T
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D015738:Famotidine / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D016595:Misoprostol / Q000627:therapeutic use; D009288:Naproxen / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000473:pathology*; D013276:Stomach Ulcer / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016595:Misoprostol; D009288:Naproxen; D015738:Famotidine