Polaprezinc Research Articles

The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats

Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint (restrained at 4 ° C for 2 h) stress induced severe hemorrhagic lesions together with increased mast cell degranulation and β-glucuronidase release in the gastric glandular mucosa. Z-103 pretreatment with a single oral dose (3, 10 or 30 mg/kg) reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10 −7, 10 −6, 10 −5 or 10 −4 M, with isolated hepatic lysosomes, it significantly reduced the spontaneous release of β-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.

Effects of zincl-carnosine on gastric mucosal and cell damage caused by ethanol in rats

The effects of zinc L-carnosine on ethanol-induced damage and the correlation of these effects with endogenous prostaglandin E2 were evaluated in rat gastric mucosa in vivo and in vitro. When given either intragastrically or intraperitoneally, zinc L-carnosine (10 or 30 mg/kg) prevented gross visible damage to gastric mucosa caused by ethanol without affecting the mucosal prostaglandin E2 level. This protective effect of zinc L-carnosine was not inhibited by indomethacin. Histological assessment showed that zinc L-carnosine inhibited deep mucosal necrosis, as did 16,16-dimethyl prostaglandin E2. Zinc L-carnosine (10(-6) or 10(-5) M) inhibited the damage caused by ethanol to gastric cells isolated from rat gastric mucosa in vitro; this effect was not inhibited by indomethacin. The results suggested that zinc L-carnosine protects the gastric mucosa and enhances cellular resistance to ethanol without the mediation of endogenous prostaglandins.

An Experimental Model for Evaluating the Protective Effects of Antiulcer Drugs

This study was undertaken in order to establish the experimental model for evaluating the protective effects of antiulcer drugs. The isolated surface epithelial cells from rat gastric mucosa were used for this experiment. One of the antiulcer drugs at a concentration of 10−7to 10−4 mol/L was added to the medium containing the cells and the cells were incubated for 10 minutes, after which alcohol was added to a final concentration of 15%. The viability of the cells was measured 10 minutes later by the trypan blue exclusion test. After isolation of the cells, their viability was about 70%, and surface epithelial cells accounted for 81% of all cells. The loss of cell viability caused by 15% alcohol was significantly inhibited by ornoprostil, misoprostol, proamipide, sofalcone, zinc l-carnosine, KW 5805 and pirenzepine. Cimetidine, ranitidine and omeprazole did not inhibit the loss of viability.

新規化合物Ｚ‐１０３の抗潰よう作用に関する研究

We investigated the anti-ulcer effects of zinc L-carnosine (Z-103) using several acute experimental models of gastric and duodenal lesions in rats. Effects of Z-103 on various gastric functions, e.g., antacid (in vitro), anti-pepsin (in vitro), gastric secretion, mucosal potential difference (PD) and mucus contents were also examined. Z-103 given orally prevented development of gastric lesions induced by water immersion stress, histamine, HCl-aspirin, HCl-ethanol and also duodenal ulcers induced by mepirizole in a dose-dependent manner. In vitro, Z-103 had a greater antacid effect than sodium bicarbonate; and moreover, the potency of its anti-peptic action (IC50 = 8.7 mM) was higher than those of several other drugs (sodium bicarbonate, sucrose sulfate and aceglutamide aluminum). Intragastric treatment of Z-103 (100 mg/kg alone tended to increase PD, and it also significantly inhibited the decrease in PD induced by aspirin. In addition, pretreatment with Z-103 at 10 and 30 mg/kg (p.o.) significantly prevented the decrease in mucus contents in the gastric mucosa and also mucosal lesions by oral administration of ethanol. On the other hand, Z-103 was not so effective on both basal (pylorus-ligation preparation) and histamine-stimulated gastric secretion (Heidenhain pouch preparation). These results suggest that Z-103 is useful for the treatment of gastric and duodenal ulcers in humans.

O-192 - Protection by zinc L-carnosine (Z-103) of gastric mucosa from damage caused by ethanol and correlation with endogenous prostaglandins

O-192 - Protection by zinc L-carnosine (Z-103) of gastric mucosa from damage caused by ethanol and correlation with endogenous prostaglandins

P-056 - Effect of a new compound, zinc L-carnosine (Z-103), on various gastric and duodenal lesions in rats

P-056 - Effect of a new compound, zinc L-carnosine (Z-103), on various gastric and duodenal lesions in rats