Gut region-specific accumulation of reactive oxygen species leads to regionally distinct activation of antioxidant and apoptotic marker molecules in rats with STZ-induced diabetes

The aim of this study was to seek possible links between the regionality along the digestive tract and the accumulation of reactive oxygen species, the effectiveness of the antioxidant defense system and the sensitivity to the types of demise in different gut regions of rats with streptozotocin-induced diabetes. Significant changes were observed in the oxidative status and in the activity of the antioxidant defense system in the diabetic colon; the peroxynitrite production was doubled, the level of hemoxygenase-2 protein was increased 11-fold and the expression of anti-apoptotic bcl-2 was also increased. The segment-specific vulnerability of the gastrointestinal tract induced by hyperglycemia was also confirmed by electron microscopy, demonstrating the presence of severe necrosis in the colon of the diabetic rats. No remarkable histopathological alterations were seen in the duodenum of the diabetic animals and there were likewise no significant changes in the production of peroxynitrite in their duodenum, whereas the level of the free radical scavenger metallothionein-2 was increased ∼300-fold. The spatially restricted vulnerability observed along the digestive tract could originate from a high level of oxidative stress via peroxynitrite production.