Aggravation of ischemia/reperfusion-induced gastric lesions in streptozotocin-diabetic rats.

We examined the influence of diabetes on ischemia/reperfusion-induced gastric damage in rats, in relation to the antioxidative system. Animals were injected with streptozotocin (STZ: 70 mg/kg, i.p.) and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Gastric mucosal blood flow (GMBF) was measured before, during and after 20 min of ischemia (1.5 ml bleeding per 100 g body weight from the carotid artery) followed by a 15-min reperfusion in the presence of acid (100 mM HCI). At the end of each experiment, gastric damage was observed macroscopically. GMBF was reduced by ischemia in all groups of rats, followed by a gradual return after reperfusion. Ischemia/reperfusion produced hemorrhagic lesions in normal rat stomachs in the presence of 100 mM HCl. These lesions were significantly aggravated when the animals were pretreated with diethyldithiocarbamate, an inhibitor of superoxide dismutase (SOD). Ischemia/reperfusion-induced damage was also markedly exacerbated in STZ-diabetic rats, but this aggravation was significantly suppressed by pretreatment with exogenous SOD or glutathione (GSH). Diabetic rat stomachs showed significantly less SOD activity as well as GSH content than normal rat stomachs. In addition, the deleterious influence of diabetes on the gastric ulcerogenic response to ischemia/reperfusion was significantly mitigated by decreasing the blood glucose levels by daily insulin treatment. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to ischemia/reperfusion-induced injury, and the mechanism may be partly accounted for by impairment of the antioxidative system associated with a reduced SOD activity and GSH content.