Gastric Injury and Protection against Alcohol and Acid: Influence of Perturbations in Glutathione Metabolism

• Published in: The Journal of surgical research 1996-03, Vol.61 (2), p.395-403
• Main Authors: Smith, Gregory S., Tornwall, Michael S., Barreto, Jose C., Miller, Thomas A.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Buthionine Sulfoximine; Ethanol - toxicity; Female; Gastric Mucosa - drug effects; Gastroenterology. Liver. Pancreas. Abdomen; Glutathione - physiology; Glutathione Peroxidase - antagonists & inhibitors; Hydrochloric Acid - toxicity; Medical sciences; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - pharmacology; Other diseases. Semiology; Rats; Rats, Sprague-Dawley; Selenium - physiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1996.0136

This study assessed the role that inhibition of glutathione (GSH) synthesis and decreased GSH peroxidase (GPX) activity in the rat played in modulating gastric injury induced by ethanol and acid and its prevention by 16,16-dimethyl PGE2(dmPGE2) and the mild irritant, 25% ethanol. Although numerous studies have proposed that GSH may be important in maintaining gastric mucosal defense, the exact role of this antioxidant in protecting the stomach from injury remains undefined. The present study addressed this consideration by blocking the synthesis of GSH and altering the major pathway by which it exhibits its antioxidant activity and determining the effect of these perturbations on gastric injury and protection. Four to six rats were used for each experimental group. GSH synthesis was blocked by the potent and specific inhibitorL-buthionine sulfoximine (BSO), 2 or 6 mmole/kg intraperitoneally. The activity of the major form of GPX, which is selenium dependent and utilizes GSH as a substrate to detoxify hydrogen peroxide and other hydroperoxides, was inhibited by placing animals on a selenium-deficient diet for 6 weeks. Gastric damage was induced by 100% ethanol, 50% ethanol in 150 mMHCl, and 0.75MHCl. Prevention of such injury was accomplished with oral pretreatment using 25% ethanol or dmPGE2(5 μg/kg). The damaging effects of 100% ethanol, 50% ethanol/150 mMHCl, or 0.75MHCl were not adversely affected by BSO pretreatment even though GSH synthesis was inhibited by as much as 80%. Similarly, inhibition of GPX activity by 58% in adult rats and 98% in weanling rats failed to potentiate the damaging effect of 100% ethanol. Furthermore, with both perturbations in GSH metabolism, the protective action of dmPGE2and 25% ethanol was maintained. Our results indicate that profound alterations in gastric GSH metabolism by themselves do not aggrevate the injurious effects of ethanol or acid, nor do they prevent the protective action of a prostaglandin or mild irritant.