Superoxide dismutase 1 and glutathione peroxidase 1 are involved in the protective effect of sulodexide on vascular endothelial cells exposed to oxygen–glucose deprivation

• SDX protects HUVEC from OGD-induced apoptosis.
• SDX attenuates ROS production and lipid peroxidation in HUVEC exposed to OGD.
• SDX increases SOD1 and GPx1 mRNA/protein expression in ischemic HUVEC.
• SDX increases SOD and GPx activity in ischemic HUVEC.
• SDX prevents of eNOS uncoupling in HUVEC exposed to OGD.

Sulodexide (SDX) is widely used in the treatment of both arterial and venous thrombotic disorders. In addition to its recognized antithrombotic action, SDX has endothelial protective potential, which is independent of the coagulation/fibrinolysis system. However, the detailed molecular mechanisms of the endothelioprotective action of the drug are still unresolved.The aim of the present study was to determine whether treatment with SDX at concentrations of 0.125–0.5 lipase releasing unit (LRU)/ml have on the expression and activity of antioxidant enzymes in ischemic endothelial cells and how these effects might be related to the antiapoptotic properties of SDX.In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to ischemia-simulating conditions (combined oxygen and glucose deprivation, OGD) for 6 h to determine the protective effects of SDX. SDX (0.25 and 0.5 LRU/ml) in OGD significantly increased the cell viability and prevented mitochondrial depolarization in the HUVECs. Moreover, SDX protected the HUVECs against OGD-induced apoptosis. At concentrations of 0.25 and 0.5 LRU/ml, the drug increased both superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1) mRNA/protein expression together with a significant attenuation of oxidative stress in ischemic HUVECs. Our findings also demonstrate that an increase in both SOD and GPx activity is involved in the protective effect of SDX on ischemic endothelial cells. Altogether, these results suggest that SDX has a positive effect on ischemia-induced endothelial damage because of its antioxidant and antiapoptotic properties.