Chronic
hyperglycemia is one of the characteristic conditions associated with
Diabetes Mellitus (DM), which often exerts deleterious effects on erythrocyte morphology and hemodynamic properties leading to
anemia and diabetes-associated vascular complications. High
glucose-induced over production of
reactive oxygen species (ROS) can alter the blood cell metabolism and biochemical functions subsequently causing eryptosis (red blood cell death), yet another complication of concern in DM. Therefore, blocking high
glucose-induced oxidative damage and subsequent eryptosis is of high importance in the better management of DM and associated vascular complications. In this study, we synthesized an oxolane derivative 1-(2,2-dimethyltetrahydrofuro[2,3][1,3]dioxol-5-yl)
ethane-1,2-diol (
DMTD), and demonstrated its efficacy to mitigate
hyperglycemia-induced ROS generation and subsequent eryptosis. We showed that
DMTD effectively inhibits high
glucose-induced ROS generation, intracellular
calcium levels, phosphaditylserine (PS) scrambling,
calpain and band 3 activation, LDH leakage, protein glycation and lipid peroxidation, meanwhile enhances the
antioxidant indices, osmotic fragility and Na+/K+-
ATPase activity in erythrocytes.
DMTD dose dependently decreased the
glycated hemoglobin level and enhances the
glucose utilization by erythrocytes in vitro. Further,
DMTD alleviated the increase in ROS production, intracellular Ca2+ level and PS externalization in the erythrocytes of human diabetic subjects and enhanced the Na+/K+-
ATPase activity. Taken together, the synthesized oxolane derivative
DMTD could be a novel synthetic inhibitor of high
glucose-induced oxidative stress and eryptosis. Considering the present results
DMTD could be a potential therapeutic to treat DM and associated complications and open new avenues in developing synthetic therapeutic targeting of DM-associated complications.