Delayed healing of gastric ulcers in adjuvant arthritis rats: role of acid secretion and basic fibroblast growth factor.
OBJECTIVE
We examined the healing process of chronic gastric ulcers in adjuvant-induced arthritic rats and investigated the mechanism for delayed ulcer healing in arthritic rats, in relation to acid secretion and basic fibroblast growth factor (bFGF).


METHODS
Arthritis was induced in male dark Agouti rats by a single injection of Freund's complete adjuvant (FCA), while gastric ulcers were induced by thermal cauterization (70 degrees C for 30 s) 7 days after FCA injection.


RESULTS
Injection of FCA induced severe arthritis in all animals with a marked acid hypersecretion. The healing of gastric ulcers was significantly delayed in arthritic rats as compared with normal rats. Daily administration of indomethacin delayed ulcer healing in both normal and arthritic rats, but this effect was more pronounced in the latter. In contrast, the healing of gastric ulcers was significantly promoted in both normal and arthritic rats by omeprazole at a dose that inhibited acid secretion completely. The delayed healing of gastric ulcers was not influenced by twice daily administration of N(G)-nitro-L-arginine methyl ester, aminoguanidine or FR167653 (IL-1/TNF-alpha synthesis inhibitor), but was significantly accelerated by CS-23 (recombinant human bFGF) in a dose-dependent manner, without effect on the acid secretion. The expression of bFGF was markedly increased after ulceration, but this response was decreased in arthritic rats.


CONCLUSIONS
The healing of gastric ulcers was delayed in arthritic rats, and this mechanism may be partly attributable to both acid hypersecretion and less expression of bFGF.
Kato
S
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan. skato@mb.kyoto-phu.ac.jp
Ogawa
Y
Y
Tanaka
A
A
Kunikata
T
T
Takeuchi
K
K
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D015153:Blotting, Western; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000032:analysis*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000150:complications* / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D016896:Treatment Outcome
D005346:Fibroblast Growth Factors; D009853:Omeprazole; D007213:Indomethacin