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

Abstract

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 β-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 β-glucuronidase. No direct effect of zinc or reserpine on purified β-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of β-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.