Gastroprotection and lysosomal membrane stabilization by sulglicotide.

Well-known agents that induce gastric ulcers cause a decrease in lysosomal stability, with release of lytic enzymes. Some antiulcer and cytoprotective agents have lysosomal membrane stabilizing activity when tested in vitro and ex vivo. Sulglicotide (Gliptide), a polysulfated glycopeptide with antiulcer and cytoprotective activities, was able to stabilize lysosomal membranes in vitro at concentrations between 9 and 36 micrograms/ml. The ratio of potency of sulglicotide to that of carbenoxolone was 12.2. In ex vivo experiments in rats, it was found that sulglicotide stabilized lysosomes after oral treatment. The effect was dose-dependent after intravenous treatment. Carbenoxolone, injected i.v. under the same experimental conditions, was less active (potency ratio 0.65). 16,16-dimethyl-PGE2, administered at a dose of 10 micrograms/kg orally or intravenously, had an activity equivalent to that of sulglicotide at a dose of 12.5 mg/kg i.v. or 200 mg/kg p.o. Sulglicotide (200-400 mg/kg p.o.) was also able to prevent the release of acid phosphatase from stomachs challenged for 10 min or 3 h with absolute ethanol. The same result was obtained with 200 mg/kg p.o. of carbenoxolone. These data show that sulglicotide is a potent lysosomal membrane stabilizer in vitro and ex vivo, and could explain the cytoprotective activity of this compound in different experimental models of ulcer.