Is omeprazole or misoprostol superior for improving indomethacin-induced delayed maturation of granulation tissue in rat gastric ulcers?
OBJECTIVE
Proton pump inhibitors (PPI) and prostaglandin (PG) preparations are believed to both prevent NSAID-induced gastric ulcers and promote the delayed healing of gastric ulcers by NSAIDs, but it remains unclear which of these drugs is superior. The aim of this study was to clarify which achieved better healing of NSAID-induced gastric ulcers, not only with respect to epithelialization but also repair of the submucosal tissues.


METHODS
We used acetic acid to induce gastric ulcers in rats, and compared the changes between a control group, NSAID group, NSAID + PPI group and NSAID + PG group. After removing the stomach of each animal, an ulcer index was calculated and the collagen content and type III collagen content of granulation tissue were measured. We also studied fibroblast dynamics, including proliferation, collagen synthesis, differentiation into myofibroblasts, and apoptosis.


RESULTS
Indomethacin prevented re-epithelialization of the ulcers, interfered with fibroblast function, and also delayed the replacement of type III collagen. Omeprazole promoted epithelialization, but could not fully reverse the influence of indomethacin on granulation tissue maturation. A concomitant dose with misoprostolreversed it completely.


CONCLUSIONS
From our point of view in this study in the use of experimental ulcers, it was thought that compensation of PG should have priority to gastric acid inhibition in terms of healing of NSAID-induced gastric ulcer.
Department of Gastroenterology, Fujita Health University, School of Medicine, Toyoake, Japan. tarisawa@fujita-hu.ac.jp
Tomiyasu
T
Arisawa
Masao
M
Harata
Yoshio
Y
Kamiya
Tomoyuki
T
Shibata
Mitsuo
M
Nagasaka
Masakatsu
M
Nakamura
Hiroshi
H
Fujita
Shin
S
Hasegawa
Masahiko
M
Nakamura
Tamaki
T
Mizuno
Tomomitsu
T
Tahara
Yoshiji
Y
Ohta
Hiroshi
H
Nakano
D000704:Analysis of Variance; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D006097:Granulation Tissue / Q000187:drug effects*; D006909:Hydroxyproline / Q000096:biosynthesis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D016595:Misoprostol / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects*
D016595:Misoprostol; D003094:Collagen; D009853:Omeprazole; D006909:Hydroxyproline; D007213:Indomethacin