Influence of prostaglandins, omeprazole, and indomethacin on healing of experimental gastric ulcers in the rat.
We investigated whether the trophic actions of prostaglandins, omeprazole, and indomethacin on gastric mucosa lead to accelerated healing of gastric ulcers in the rat. Cryoulcers were produced in the corpus area and treated with 16,16-dimethyl prostaglandin E2 (5 or 100 micrograms/kg b.i.d., intragastrically), omeprazole (40 mumol/kg once daily, subcutaneously), indomethacin (2 mg/kg b.i.d., subcutaneously), or placebo. At the end of the treatment, plasma gastrin, cell labeling index (autoradiography with [3H]thymidine), and the size and depth of mucosal defects were measured. Compared with placebo, omeprazole accelerated ulcer healing as indicated by a smaller ulcer area [1.1 +/- 0.2 vs. 4.8 +/- 1.2 mm2 (mean +/- SEM)] and smaller ulcer depth (383 +/- 31 vs. 488 +/- 41 microns) after 10 days of treatment. Prostaglandins did not affect ulcer healing despite thickening of gastric corpus mucosa. Indomethacin delayed ulcer healing and reduced the labeling index. Omeprazole induced a marked hypergastrinemia (208 +/- 12 vs. 66 +/- 12 pmol/L on day 5, and 469 +/- 23 vs. 58 +/- 16 pmol/L on day 10). The results indicate that abolishment of acid secretion by omeprazole accelerates healing. Trophic actions and "cytoprotective" effects by prostaglandins are not relevant for ulcer healing in this model.
Inauen
W
W
Gastrointestinal Unit, Inselspital Bern, Switzerland.
Wyss
P A
PA
Kayser
S
S
Baumgartner
A
A
Schürer-Maly
C C
CC
Koelz
H R
HR
Halter
F
F
D015064:16,16-Dimethylprostaglandin E2 / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001345:Autoradiography; D001835:Body Weight; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000097:blood; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use*; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D005755:Gastrins; D011459:Prostaglandins E, Synthetic; D009853:Omeprazole; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin