PROTECTION AGAINST ETHANOL INJURY IN THE CANINE STOMACH - ROLE OF MUCOSAL GLUTATHIONE

The present study determined the role that mucosal glutathione (GSH) levels play in mediating the protective effects of a prostaglandin and a mild irritant against alcohol-induced gastric injury. An in vivo canine chambered stomach preparation was used in which the exteriorized mucosa was partitioned into two equal halves, one serving as control. Animals (5-8/group) received a subcutaneous injection of either normal saline (NS) or the GSH depletor N-ethylmaleimide (NEM; 50 mg/kg) and then were assigned to one of a variety of groups based on the perfusate used to bathe the experimental side of the chamber; NS bathed the control mucosa. At completion of the studies, mucosa from each side of the chamber was assayed for total GSH (mu-mol/g wet wt) and evaluated for microscopic damage. Both 16,16-dimethyl prostaglandin E2 (PGE2) (1-mu-g/ml) and the mild irritant 8% ethanol, when topically applied to the gastric epithelium, increased mucosal GSH levels by approximately 20% compared with control values, and elicited no deleterious effects to the mucosa. Treatment of animals with NEM prevented these GSH effects by PGE2 and 8% ethanol without damaging the mucosa. Application of 40% ethanol to the mucosa markedly reduced levels of GSH and caused significant injury to the mucosal surface, much of it extending to the level of the gastric glands. When mucosa was pretreated with PGE2 or 8% ethanol before 40% ethanol exposure, deep gastric gland injury was virtually abolished. In animals receiving NEM, the protective effects of these agents against injury by 40% ethanol were prevented. Perturbations in tissue levels of GSH under these various experimental conditions failed to correlate histologically with the status of gastric mucosal integrity. We conclude that while PGE2 and 8% ethanol enhanced GSH levels in gastric mucosa, possibly by inducing synthesis of GSH, this circumstance did not account for the ability of these agents to enable the mucosa to resist the deep damage elicited by 40% ethanol.