Does Hyperglycemia Cause Oxidative Stress in the Diabetic Rat Retina?

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-04, Vol.10 (4), p.794
• Main Author: Ola, Mohammad Shamsul
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Carbon dioxide; Citric acid; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - pathology; Diabetic retinopathy; Enzymes; Free radicals; Glucose; Glucose - metabolism; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Hyperglycemia; Hyperglycemia - complications; Hyperglycemia - pathology; Kinases; Metabolic disorders; Metabolism; Metabolites; Mitochondria; Oxidation; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Pathophysiology; Proteins; Rats; Rats, Wistar; Reactive oxygen species; Retina; Retina - drug effects; Retina - pathology; Retinopathy; Rodents; Streptozocin; Tricarboxylic acid cycle
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10040794

Diabetes, being a metabolic disease dysregulates a large number of metabolites and factors. However, among those altered metabolites, hyperglycemia is considered as the major factor to cause an increase in oxidative stress that initiates the pathophysiology of retinal damage leading to diabetic retinopathy. Diabetes-induced oxidative stress in the diabetic retina and its damaging effects are well known, but still, the exact source and the mechanism of hyperglycemia-induced reactive oxygen species (ROS) generation especially through mitochondria remains uncertain. In this study, we analyzed precisely the generation of ROS and the antioxidant capacity of enzymes in a real-time situation under ex vivo and in vivo conditions in the control and streptozotocin-induced diabetic rat retinas. We also measured the rate of flux through the citric acid cycle by determining the oxidation of glucose to CO and glutamate, under ex vivo conditions in the control and diabetic retinas. Measurements of H O clearance from the ex vivo control and diabetic retinas indicated that activities of mitochondrial antioxidant enzymes are intact in the diabetic retina. Short-term hyperglycemia seems to influence a decrease in ROS generation in the diabetic retina compared to controls, which is also correlated with a decreased oxidation rate of glucose in the diabetic retina. However, an increase in the formation of ROS was observed in the diabetic retinas compared to controls under in vivo conditions. Thus, our results suggest of diabetes/hyperglycemia-induced non-mitochondrial sources may serve as major sources of ROS generation in the diabetic retina as opposed to widely believed hyperglycemia-induced mitochondrial sources of excess ROS. Therefore, hyperglycemia per se may not cause an increase in oxidative stress, especially through mitochondria to damage the retina as in the case of diabetic retinopathy.