INTRAGASTRIC POLYETHYLENE GLYCOL-400 PROTECTS AGAINST ETHANOL-INDUCED GASTRIC-MUCOSAL LESIONS DESPITE PRETREATMENT WITH INDOMETHACIN OR IODOACETAMIDE

It has been shown that intragastric administration of polyethylene glycol-400 (PEG-400) by gavage needle protected the rat gastric mucosa from 96% ethanol-induced lesions in a dose-dependent fashion. The inhibitions of the lesions were 10.5, 53.5, 94.6, and 99.2% at doses of 275, 1375, 2750, and 5500 mg/kg, respectively. The duration of the protective effect was approximately 12 hr. The gastroprotection offered by PEG-400 was not modified by pretreatment with either subcutaneous indomethacin (25 mg/kg) or iodoacetamide (100 mg/kg). Gastric motility, measured by a balloon method, was dose-dependently inhibited by intragastric administration of PEG-400. The inhibited gastric motility (amplitude gastric contraction) induced by PEG-400 was not modified by pretreatment with either indomethacin or iodoacetamide. The gastric emptying rate, investigated by measuring the disappearance of intragastrically administered [Tc-99m]DTPA from the stomach of rats treated with PEG-400 (5500 mg/kg) was markedly retarded. There was an increase in both the fluid volume and the mucus volume retained in the gastric lumen only for PEG-400 (5500 mg/kg) at 1, 2, and 4 hr after administration. The rats treated with 0.7 ml of vehicle plus 96% ethanol had significantly less damage than those treated with 0.2 ml of vehicle plus 96% ethanol. These results indicate that intragastric PEG-400-protective effect was not mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, or changes in gastric contractile patterns. We conclude that the protective effect of intragastric PEG-400 may be the result of retarded gastric emptying together with an osmotic pull of fluid into the stomach and the increase in gastric mucus volume. However, the possibility that intragastric PEG-400 also may have the capacity to stabilize or augment the stomach's hydrophobic properties cannot be excluded.