Effect of polaprezinc on impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats--role of insulin-like growth factors (IGF)-1.
Polaprezinc, N-(3-aminopropionyl)-L-histidinatozinc, has been shown to stimulate the production of insulin-like growth factor-1 (IGF-1) in mesenchymal cells, the polypeptide playing a role in the gastric epithelial wound repair. The present study was performed to examine the effect of polaprezinc on the impaired healing of chronic gastric ulcers in adjuvant-induced arthritic rats, in relation to IGF-1. Arthritis was induced in male Dark Agouti (DA) rats by a single injection of Freund's complete adjuvant (FCA), and the gastric ulcers were induced by thermal cauterization (70 degrees C for 30 sec) 7 days after FCA injection. Omeprazole (30 mg/kg) was administered p.o. once daily, while recombinant human IGF-1 (rhIGF-1) (30 micrograms/kg, s.c.) or polaprezinc (3-10 mg/kg, p.o.) was administered twice daily, starting from 3 days after ulceration for 14 days. The healing of gastric ulcers was significantly delayed in arthritic rats as compared to normal rats on day 10 and 17 following ulceration. The expression of IGF-1 mRNA was markedly increased in the ulcerated mucosa, but this response was apparently attenuated in arthritic rats. Repeated administration of polaprezinc accelerated the healing of gastric ulcers in both normal and arthritic rats, in a dose-dependent manner, and this effect was more pronounced in arthritic rats. Likewise, treatment with omeprazole also significantly promoted the healing of gastric ulcers in both normal and arthritic rats. On the other hand, rhIGF-1 significantly promoted the gastric ulcer healing in arthritic rats without any effect on that in normal rats. These results suggest that the impaired healing of chronic gastric ulcers in arthritic rats is, at least partly, accounted for by less expression of IGF-1, and the polaprezinc improves the delayed healing of gastric ulcers in arthritic rats, probably through an increase in IGF-1 production.
Kato
S
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan. skato@mb.kyoto-phu.ac.jp
Tanaka
A
A
Ogawa
Y
Y
Kanatsu
K
K
Seto
K
K
Yoneda
T
T
Takeuchi
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000150:complications / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D002336:Carnosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002425:Cautery; D004487:Edema / Q000503:physiopathology; D005620:Freund's Adjuvant; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013276:Stomach Ulcer / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D012333:RNA, Messenger; D011994:Recombinant Proteins; D017967:Zinc Compounds; C061957:polaprezinc; D007334:Insulin-Like Growth Factor I; D002336:Carnosine; D005620:Freund's Adjuvant; D009853:Omeprazole