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Hyperglycemia is a state in which excess glucose circulates in blood. Erythrocytes are in direct contact with this high glucose concentration and are greatly affected by it. We have examined the effect of hyperglycemic condition on isolated human erythrocytes under in vitro conditions. Erythrocytes were incubated with different concentrations of glucose (5, 15, 30, 45 mmol/L) for 24 h, and several biochemical parameters were determined. Treatment with high glucose concentrations increased heme degradation and methemoglobin level, while methemoglobin reductase activity was decreased. A significant increase in protein oxidation and lipid hydroperoxides with a decrease in total sulfhydryl content was seen. This suggested the generation of oxidative stress, which was confirmed by an enhanced production of reactive oxygen and nitrogen species. Hyperglycemia led to a significant decline in the antioxidant …