Indomethacin-induced morphological changes in the rat gastric mucosa, with or without prior treatment with two proton pump inhibitors.
BACKGROUND
The mechanisms responsible for the gastric ulcerogenic effect of indomethacin are unclear. The importance of basal acid secretion on morphological changes by indomethacin was investigated.


METHODS
Gastric lesions were macroscopically evaluated 6 h after indomethacin, 20 mg/kg intragastrically, in rats pre-treated with omeprazole (10-100 mumol/kg intragastrically) or lansoprazole (3-30 mumol/kg intragastrically). Glandular mucosa was processed for light, scanning and transmission electron microscopy 3 and 6 h after indomethacin in rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg).


RESULTS
After 3 h, indomethacin caused extensive vasocongestion, oedema in the subepithelial region and superficial erosions. After 6 h, deeply extending focal necrosis involved 11% of the tissue. Leukocyte margination was occasionally seen at 3 h and consistently present at 6 h. Only at 6 h were endothelial cells altered. In rats pre-treated with omeprazole (100 mumol/kg) or lansoprazole (30 mumol/kg) grossly visible lesions were prevented. Oedema, erosions and necrosis were absent. Vasocongestion, vascular leakage and leukocytic margination were seen both at 3 and 6 h while no major damage of endothelial cells was observed.


CONCLUSIONS
Indomethacin appears primarily to alter microcirculation, and microcirculation damage is dependent on acid for the progression to haemorrhagic lesions.
Morini
G
G
Institute of Pharmacology, University of Parma, Italy.
Grandi
D
D
Arcari
M L
ML
Bertaccini
G
G
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity*; D064747:Lansoprazole; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000098:blood supply / Q000187:drug effects*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D009853:Omeprazole; D007213:Indomethacin