Possible mechanisms of diethyldithiocarbamate-induced duodenal mucosal damage in rats.
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概要
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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 aggresive and defensive factors. Possible importance of oxygen-derived free radicals was also investigated.Male Wistar rats weighing about 200g received a single subcutaneous injection of DDC at a dose of 1g/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±2.6μEq/kg/h (m±SE) 30 minutes after the administration of DDC (p<0.01), which gradually recovered thereafter. Duodenal mucosal blood flow before DDC injection was 144.7±12.7ml/min/100g, which decreased to 83.3±5.1 (p<0.01) 1 hour later. Transmucosal potential difference of the duodenum before DDC injection was -9.5±1.0mV, which decreased to -3.8±1.3 (p<0.05) 30 minutes later. Duodenal alkaline secretion before DDC injection was 15.6±0.8μEq/kg/h, which decreased to 5.0±0.9μEq/kg/h (p<0.01) 90 minutes later. PAS-stained mucus of Brunner's glands remained unchanged by the administraiton of DDC. SOD activity was markedly inhibited from 57.7±4.0 to 15.7±0.9u/mg protein 3 hours after the administration of DDC (p<0.01), then recovered 24 hours later. Catalase and glutathione peroxidase activity, which scavenge hydrogen peroxide, gradually increased from 12 hours.These results suggest that the decrease of mucosal defensive mechanisms such as gastroduodenal mucosal blood flow and potential difference play an important role in the development of duodenal mucosal damage induced by DDC. Oxygen-derived free radicals may also participate in the develpment of this mucosal damage.
- 財団法人 日本消化器病学会の論文
著者
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高升 正彦
京都府立医科大学第3内科
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布施 好信
京都府立医科大学第3内科
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小原 尚之
京都府立医科大学第3内科
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布施 好信
京都府立医科大学第2病理
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川本 克久
京都府立医科大学第3内科
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児玉 正
京都府立医科大学第3内科
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