Role of superoxide dismutase in mechanism of diethyldithiocarbamate-induced gastric antral ulcer in rats: protective effect of prostaglandin, cimetidine and pirenzepine.

The role of superoxide radicals and the protective effects of superoxide dismutase (SOD), allopurinol, 16,16-dimethyl-prostaglandin E2 (dmPGE2), cimetidine and pirenzepine in diethyldithiocarbamate (DDC)-treated rats were evaluated. Pretreatment with Cu,Zn-SOD (superoxide radical scavenger) 60,000 units/kg, allopurinol (competitive inhibitor of xanthine oxidase) 50 mg/kg, dmPGE2 (prostaglandin analogue) 10 micrograms/kg, cimetidine (H2-receptor antagonist) 10 mg/kg or pirenzepine (selective antimuscarinic drug) 10 mg/kg all significantly reduced the DDC-induced (800 mg/kg) gastric antral ulcer formation in rats. DDC treatment substantially decreases the gastric mucosal Cu,Zn-SOD activity. In this study treatment with DDC and SOD, DDC and dmPGE2, DDC and cimetidine, and DDC and pirenzepine were demonstrated significantly to prevent the decrease of gastric mucosal Cu,Zn-SOD activity. However, allopurinol did not have this effect. The results suggest that SOD and/or superoxide radicals may play an important role in the mechanism of DDC-induced gastric antral ulcer. The protective property against ulcer formation of these drugs studied might be due to the action of SOD in the gastric mucosa.