Mechanism of diethyldithiocarbamate-induced gastric ulcer formation in the rat.

Diethyldithiocarbamate (DDC) was injected subcutaneously in the rat and the mechanism of gastric ulcer formation was investigated. DDC induced gastric ulcers in a dose-dependent manner. DDC significantly suppressed gastric mucosal copper-zinc superoxide dismutase (Cu, Zn-SOD) activity at 2 hr. However, manganese-superoxide dismutase (Mn-SOD) activity was not changed. Gastric mucosal blood flow (GMBF) decreased to 52% of the control level at 2 hr after administration of DDC and gradually increased to reach the control level by 7 hr. A Shay rat preparation (4 hr) was used to study gastric secretion. DDC (200, 400 and 800 mg/kg) inhibited acid secretion to about 80% of the control level. Histopathological examination of the gastric mucosa after administration of DDC revealed mucosal congestive findings from 1 hr to 3 hr. These data suggested that the mechanism of DDC-induced gastric ulcer formation may be attributable to a decreased level of GMBF and O2- production owing to decreased SOD activity.