Combined effects of polaprezinc (Z-103) and cimetidine on gastric duodenal lesions in rats

Combined effects of polaprezinc (Z-103) and cimetidine on several experimental models of gastric and duodenal lesions, were investigated in rats. Z-103 (1 ~ 10 mg/kg), but not cimetidine (100 mg/kg), prevented the developmental of acidified ethanol induced gastric lesions. Effect of Z-103 in combination with cimetidine were more potent than those of Z-103 alone. Z-103 (3 ~ 30 mg/kg) and cimetidine (30 mg/kg) prevented the development of gastric and duodenal lesions induced by water-immersion stress, indomethacin and mepirizole. The inhibitory effect of Z-103 was increased by the combined use with cimetidine. In acetic acid induced gastric ulcers, the combined administration of Z-103 (0.3 ~ 3 mg/kg) and cimetidine (100 mg/kg) potentiated the ulcer healing in comparison with each drug alone. The inhibitory effect of cimetidine (30 or 100 mg/kg) in the basal acid secretion was not influenced by the combine treatment of Z-103 (1 ~ 30 mg/kg). The increase in TBA-reactive substances, as index of lipid peroxidation, and free β-glucuronidase activity, as index of membrane stabilizing action, in gastric mucosa after water-immersion stress, were significantly inhibited by the administration of Z-103 (3 ~ 30 mg/kg). In addition, these effects of Z-103 were increased by the combined use with cimetidine (30 mg/kg). On the 1st day after the cessation of 14 day-consecutive treatment with cimetidine (100 mg/kg x 2/day) and Z-103 (1 or 3 mg/kg x 2/day), cimetidine, but not Z-103, significantly increased acidified ethanol-induced gastric lesions as compared with the control. However, with the co-administration of Z-103 and cimetidine, the gastric lesions were significantly decreased as compared with those of the cimetidine alone. These results suggest that the combination of Z-103 and a H₂-receptor antagonist such as cimetidine, may be more effective for the treatment of gastric lesions in clinical therapy.