Reserpine-induced gastric ulcers: protection by lysosomal stabilization due to zinc

The effects of graded doses of zinc sulfate pretreatment on reserpine-induced gastric ulceration and on lysosomal fragility both in vivo and in vitro, were studied in rats. Reserpine treatment (5 mg/kg, i.p., 18 h before sacrifice) induced marked gastric glandular ulceration and elicited the release of free beta-glucuronidase from lysosomes in the gastric mucosa. A similar effect on release of this enzyme from isolated rat hepatic lysosomes was observed after in vitro incubation with reserpine. Zinc sulfate (22, 44 or 88 mg/kg, i.p., 30 h before reserpinization, or 10(-3) M in vitro) inhibited the reserpine-induced response, and zinc sulfate alone (10(-11)--10(-3) M) also stabilized lysosomal membrane permeability to beta-glucuronidase. No direct effect of zinc or reserpine on purified beta-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of beta-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.