Gastric mucosal damage induced by 2-deoxy-D-glucose involves medullary TRH in the rat

These studies examined the effect of 2-deoxy-D-glucose (2-DG) on gastric mucosal integrity. Intravenous administration of 2-DG in doses of 100 and 125 mg/kg dose-dependently produced multiple, hemorrhagic gastric mucosal lesions while 75 mg/kg of 2-DG failed to induce gastric lesions. Intracisternal injection of 2-DG in doses of 10 and 20 mg/kg also induced gastric mucosal damage in a dose-dependent manner whereas the injection of 5 mg/kg of 2-DG intracisternally did not induce the development of gastric lesions. Gastric mucosal damage by intravenous 2-DG was completely blocked by bilateral gastric branch vagotomy. Intracisternal but not intraperitoneal injection of anti-TRH antibody 8964 significantly reduced the severity of gastric mucosal lesions evoked by intravenous administration of 2-DG. These results suggest that 2-DG acts in the brain to induce gastric mucosal damage through vagal dependent pathways. Endogenous TRH in the central nervous system may be involved in the production of gastric mucosal damage by 2-DG.