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.