PROTECTION OF GASTRIC-MUCOSA AGAINST ETHANOL-INDUCED INJURY BY INTRAGASTRIC BOLUS ADMINISTRATION OF EPIDERMAL GROWTH-FACTOR COMBINED WITH HYDROXYPROPYLCELLULOSE

Orally administered epidermal growth factor (EGF) has been shown to protect the gastric mucosa against injury induced by noxious agents. However, EGF administered by intragastric bolus appears to have less effect on the gastric mucosa because of its rapid excretion from the gastric lumen. In this study, mouse EGF given to rats by gastric intubation was confirmed to remain in the stomach at significantly high concentrations when given in combination with hydroxypropylcellulose (HPC), an agent that retards drug release. The residual mouse EGF levels in the gastric luminal content and tissue 3 h after administration of 50-mu-g/kg of EGF dissolved in 1 ml of 2% HPC were 30 and 60 times higher, respectively, than those obtained after EGF alone. Pretreatment with intragastric bolus administration of EGF and HPC at the same dose for 3 h attenuated significantly the development of gastric lesions induced by absolute ethanol compared to that with HPC alone, EGF alone, or saline (mean values of ulcer index: EGF + HPC, 14.3; HPC, 52.8; EGF, 50.7; and saline, 63.2 mm). There were no significant differences between the ulcer index in the HPC, EGF, and saline groups. The present study indicates that exogenous EGF given as an intragastric bolus protects the gastric mucosa against injury when combined with HPC, which can bind to EGF and prevent its rapid excretion from the gastric lumen.