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

High Sensitivity of Gastric Mucosa to Ulcerogenic Effect of Indomethacin in Rats with Diabetes

“…However, in contrast to published data, according to which the sensitivity of the gastric mucosa to ulcerogenic factors increased only 3-5 weeks after streptozotocin injection [11,13], our results indicated that diabetes enhanced gastric mucosa sensitivity to indomethacin injected in an ulcerogenic dose to rats after 24-h fasting as early as just 1 week after streptozotocin injection.…”

“…This increases its sensitivity to such ulcerogenic exposures as fasting [9,12], cooling [8], ischemiareperfusion of the stomach [13], and inhibits healing of gastric mucosa lesions [3,7]. The destructive effect of diabetes on the stomach was observed not before 3-5 weeks after streptozotocin injection.…”

Redox biology of the intestine

“…However, diabetes associated hyperglycemia, oxidative and carbonyl stress can augment the susceptibility of the gastrointestinal system to oxidant- or ischemia/reperfusion-induced damage [234,235]. Significantly, diabetic rats exhibit impaired antioxidant defense capacity, evidenced by lower mucosal SOD activity and depressed GSH levels [234,236].…”

“…However, diabetes associated hyperglycemia, oxidative and carbonyl stress can augment the susceptibility of the gastrointestinal system to oxidant- or ischemia/reperfusion-induced damage [234,235]. Significantly, diabetic rats exhibit impaired antioxidant defense capacity, evidenced by lower mucosal SOD activity and depressed GSH levels [234,236]. In accordance with an increased capacity to scavenge ROS, the administration of SOD or GSH was able to reverse oxidant-mediated gastrointestinal injury [234] while GSH depletion via starvation induced gastric lesions in streptozotocin-treated diabetic rats [237].…”

“…Significantly, diabetic rats exhibit impaired antioxidant defense capacity, evidenced by lower mucosal SOD activity and depressed GSH levels [234,236]. In accordance with an increased capacity to scavenge ROS, the administration of SOD or GSH was able to reverse oxidant-mediated gastrointestinal injury [234] while GSH depletion via starvation induced gastric lesions in streptozotocin-treated diabetic rats [237]. Importantly, the intestinal capacity for ROS elimination are majorly influenced by factors that modulate mucosal GSH regeneration, including glucose availability, cysteine supply, and NADPH production [237], rather than the activities of “core” redox enzymes such as Gpx, GR, and glucose-6-phosphate Surprisingly, glycemic control by short-term insulin treatment decreased mucosal GSH and suppressed activities of these core enzymes which were reversed by 7-day insulin treatment [235], suggesting a heightened vulnerability of the diabetic intestine to acute glycemic fluctuation.…”