PMID- 10857004
OWN - NLM
STAT- MEDLINE
DCOM- 20000707
LR  - 20131121
IS  - 1532-0820 (Print)
IS  - 1532-0820 (Linking)
VI  - 50
IP  - 2
DP  - 2000 Apr
TI  - Role of cytoprotectants and nitric oxide inhibition in nonsteroidal 
      anti-inflammatory drug-induced gastroduodenal injury in the rat.
PG  - 140-6
AB  - BACKGROUND AND PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce 
      gastroduodenal injury and ulceration. The pathogenesis is uncertain, although 
      reductions in cytoprotective prostaglandins and nitric oxide (NO) have been 
      proposed. The effects of several cytoprotective agents on inhibition of 
      gastroduodenal ulcerogenesis induced by CI-987, a novel NSAID, were evaluated in 
      Wistar rats. METHODS: Male Wistar rats were given CI-987 orally (p.o.) at a 
      dosage of 300 or 450 mg/kg of body weight or subcutaneously (s.c.) (3 x 50 
      mg/kg), alone or with misoprostol pretreatment (2 x 1 mg/kg, p.o.). In a second 
      experiment, rats were pre-treated with 2 ml of gelusil p.o., 500 mg of 
      sucralfate/kg, p.o., 100 mg of ranitidine/kg s.c., or 200 mg of N 
      omega-nitro-L-arginine methyl ester (L-NAME)/kg, s.c.. Duodenal injury was 
      induced by administration of 450 mg of CI-987/kg, p.o., 3 x 50 mg of CI-987/kg, 
      s.c., or 300 mg of cysteamine/kg, s.c. Animals were euthanized within 24 to 48 
      hours, and the gastrointestinal tract was examined for evidence of gross or 
      microscopic change. RESULTS: The L-NAME significantly reduced the incidence and 
      severity of gastroduodenal injury induced by CI-987 and cysteamine. Prostaglandin 
      ameliorated duodenal lesions induced by CI-987 given s.c., and Gelusil, 
      ranitidine, and sucralfate were without effect on duodenal lesions induced by 
      NSAID. CONCLUSIONS: Preemptive blockade of NO synthase is important in preventing 
      NSAID-induced duodenal injury in rats. Inhibition of cytoprotective 
      prostaglandins and enhanced acid-induced damage are unlikely to be primary 
      mechanisms underlying NSAID-induced duodenal injury in rats.
FAU - Turner, P V
AU  - Turner PV
AD  - Parke-Davis Research Institute, Mississauga, Ontario, Canada.
FAU - Albassam, M A
AU  - Albassam MA
FAU - Percy, D H
AU  - Percy DH
FAU - Lillie, L E
AU  - Lillie LE
FAU - Macallum, G E
AU  - Macallum GE
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Comp Med
JT  - Comparative medicine
JID - 100900466
RN  - 0 (Antacids)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (CI 987)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phenols)
RN  - 0 (Thiazoles)
RN  - 0E43V0BB57 (Misoprostol)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 54182-58-0 (Sucralfate)
RN  - 5UX2SD1KE2 (Cysteamine)
RN  - 884KT10YB7 (Ranitidine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - F5TD010360 (Alprostadil)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Administration, Oral
MH  - Alprostadil/analogs & derivatives/pharmacology
MH  - Animals
MH  - Antacids/administration & dosage
MH  - Anti-Inflammatory Agents, Non-Steroidal
MH  - Anti-Ulcer Agents/*pharmacology
MH  - Cyclooxygenase Inhibitors
MH  - Cysteamine/administration & dosage
MH  - *Cytoprotection
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Enzyme Inhibitors/administration & dosage
MH  - Injections, Subcutaneous
MH  - Male
MH  - Misoprostol/pharmacology
MH  - NG-Nitroarginine Methyl Ester/administration & dosage
MH  - Nitric Oxide/*antagonists & inhibitors
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Phenols
MH  - Ranitidine/administration & dosage
MH  - Rats
MH  - Rats, Wistar
MH  - Sucralfate/administration & dosage
MH  - Thiazoles
EDAT- 2000/06/17 09:00
MHDA- 2000/07/15 11:00
CRDT- 2000/06/17 09:00
PHST- 2000/06/17 09:00 [pubmed]
PHST- 2000/07/15 11:00 [medline]
PHST- 2000/06/17 09:00 [entrez]
PST - ppublish
SO  - Comp Med. 2000 Apr;50(2):140-6.