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Abstract

Long-term complications of diabetes mellitus have been ascribed to both the effects of prolonged hyperglycemia and to increased oxidative stress. In an attempt to identify the mechanisms underlying the acute effects of hyperglycemia on oxidative stress, we investigated the hypothesis that high glucose might lead to an insufficiency in reducing equivalents (such as NADPH) and thus to a disruption in the glutathione-dependent antioxidant defences and to an incapacity to deal with oxidant attack. For this purpose, erythrocytes from diabetic patients were incubated for 0-90 min in 5.55 or 33.3 mM D-glucose containing tertbutyl hydroperoxide 0.5 and 1 mM, Menadione 100 microM, or glucose oxidase. The time course of the changes in non-protein bound glutathione (reduced and oxidised), lactate and pyruvate, alanine and fluorescent products of oxidative proteolysis, hemolysis and methemoglobin was monitored. The results show that although glucose utilisation was unaffected, all oxidants caused a persistent decrease in total non-protein-bound glutathione suggesting binding to proteins. However, changes in glutathione and redox status differed between the various oxidants and were not directly related to the extent of oxidative cellular damage. In these experimental conditions, with short incubations and using the erythrocyte as the simplest cellular model of glucose metabolism, neither high glucose nor the diabetic condition worsened the susceptibility of erythrocytes to acute in vitro oxidative damage.

Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis

“…These enzymes are the first line of defence against ROS and reactive nitrogen species (RNS), and their alteration directly impacts the intracellular antioxidant potential of erythrocytes by increasing the GSSG/GSH ratio. The glutathione (GSH) of erythrocytes is considered the most abundant circulating antioxidant pool in the body [ 176 ]. Reduced glutathione could neutralize superoxide products that give rise to the formation of oxidation products, including glutathione disulphide (GSSG).…”