Abstract
We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks). These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively) production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III) and cytochrome c oxidase (Complex IV) were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I) and succinate:ubiquinone oxidoreductase (Complex II) were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.
Highlights
Increased oxidative stress has been implicated in the etiology and pathology of diabetic complications [1,2,3]
We have previously shown that increased superoxide production during the early stages of STZ-induced diabetes (4 weeks) is in part related to decreased GSH pool and altered electron flow from NADH in the mitochondria [23]
The values for diabetic rats were calculated from 4 rats that maintained chronic hyperglycemia throughout the experiment
Summary
Increased oxidative stress has been implicated in the etiology (especially type 1) and pathology (both type 1 and type 2) of diabetic complications [1,2,3]. Hyperglycemia, increased production of reactive oxygen and nitrogen species (ROS and RNS), increased protein glycation, increased lipolysis, ketogenesis and decreased antioxidants, glutathione (GSH) and NAD(P)H have all been reported to be involved [4,5,6,7,8]. It is suggested that suppression of oxidative stress in beta cells may prevent or delay the onset of type 1 and progression of type 2 diabetes and related complications. Several studies have shown that treatment with antioxidants protects against the onset of diabetes [10,11,12]
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