[Possible mechanisms of diethyldithiocarbamate-induced duodenal mucosal damage in rats]

Diethyldithiocarbamate (DDC), which markedly lowers activity of Cu, Zn-superoxide dismutase (SOD), induces not only gastric but also duodenal mucosal damage in rats. In this experiment, we studied on the mechanisms of DDC-induced duodenal mucosal damage with special reference to aggressive and defensive factors. Possible importance of oxygen-derived free radicals was also investigated. Male Wistar rats weighing about 200 g received a single subcutaneous injection of DDC at a dose of 1 g/kg. Mucosal lesions such as edema, shortness of villi and shallow erosion developed from 3 hours after DDC injection. The ulcer index reached at its maximum 12 hours later. Gastric acid output was markedly inhibited from 87.7 +/- 8.7 to 14.0 +/- 2.6 microEq/kg/h (m +/- SE) 30 minutes after the administration of DDC (p less than 0.01), which gradually recovered thereafter. Duodenal mucosal blood flow before DDC injection was 144.7 +/- 12.7 ml/min/100 g, which decreased to 83.3 +/- 5.1 (p less than 0.01) 1 hour later. Transmucosal potential difference of the duodenum before DDC injection was -9.5 +/- 1.0 mV, which decreased to -3.8 +/- 1.3 (p less than 0.05) 30 minutes later. Duodenal alkaline secretion before DDC injection was 15.6 +/- 0.8 microEq/kg/h, which decreased to 5.0 +/- 0.9 microEq/kg/h (p less than 0.01) 90 minutes later. PAS-stained mucus of Brunner's glands remained unchanged by the administration of DDC. SOD activity was markedly inhibited from 57.7 +/- 4.0 to 15.7 +/- 0.9 u/mg protein 3 hours after the administration of DDC (p less than 0.01), then recovered 24 hours later.(ABSTRACT TRUNCATED AT 250 WORDS)