Glyprolines have been reported to exert protective effects in the stomach. In this study, we examined the potential effects of
intranasal administration of
Pro-Gly-Pro (PGP) and N-acetyl-
Pro-Gly-Pro (AcPGP) on experimental
gastric ulcer formation and healing. We also studied gastric release of the
cytokine GRO/CINC-1, and its potential role in
ulcer development and healing.
Gastric ulcers were induced in rats by applying
acetic acid to the serosa of the stomach. PGP and AcPGP were then administered at a dose of 3.7 μmol/kg once daily on either days 1 - 3 (
ulcer formation) or days 4 - 6 (
ulcer healing). Measurement of
ulcer area and histological examination of gastric tissue were carried out on days 4 and 7 after application of
acetic acid. In vitro studies involved addition of the glyprolines to cultured rat gastric epithelial cells with or without
lipopolysaccharide. Reverse transcription PCR, real-time PCR and ELISA were used for
cytokine analysis. PGP and AcPGP significantly reduced
ulcer areas on the 4(th) day and accelerated the healing on the 7(th) day compared with the control. After
acetic acid-induced ulceration, the expression of GRO/CINC-1
mRNA in gastric tissue was increased 9-fold versus the
sham-operated group. Treatment with PGP or AcPGP both significantly suppressed the expression of GRO/CINC-1
mRNA in gastric tissue. However, the glyprolines did not alter LPS-induced
mRNA expression or release of GRO/CINC-1 from cultured rat gastric epithelial cells, even though those cells were harvested from rats subjected to the
ulcer-induction procedure. The results of this study show that
intranasal administration of PGP and AcPGP significantly increased resistance against
acetic acid-induced ulceration and accelerated healing in the rats. These effects may be due, at least in part, to their ability to reduce the
acetic acid-induced GRO/CINC-1 expression and production in gastric tissue.