glucuronyl-glucosamine-glycan-sulfate and Ischemia

Sulodexide (SDX), a purified glycosaminoglycan mixture used to treat vascular diseases, has been reported to exert endothelial protective effects against ischemic injury. However, the mechanisms underlying these effects remain to be fully elucidated. The emerging evidence indicated that a relatively high intracellular concentration of reduced glutathione (GSH) and a maintenance of the redox environment participate in the endothelial cell survival during ischemia. Therefore, the aim of the present study was to examine the hypothesis that SDX alleviates oxygen-glucose deprivation (OGD)-induced human umbilical endothelial cells' (HUVECs) injury, which serves as the in vitro model of ischemia, by affecting the redox state of the GSH: glutathione disulfide (GSSG) pool. The cellular GSH, GSSG and total glutathione (tGSH) concentrations were measured by colorimetric method and the redox potential (ΔEh) of the GSSG/2GSH couple was calculated, using the Nernst equation. Furthermore, the levels of the glutamate-cysteine ligase catalytic subunit (GCLc) and the glutathione synthetase (GSS) proteins, a key enzyme for de novo GSH synthesis, were determined using enzyme-linked immunoassay (ELISA). We demonstrated that the SDX treatment in OGD conditions significantly elevated the intracellular GSH, enhanced the GSH:GSSG ratio, shifting the redox potential to a more pro-reducing status. Furthermore, SDX increased the levels of both GCLc and GSS. The results show that SDX protects the human endothelial cells against ischemic stress by affecting the GSH levels and cellular redox state. These changes suggest that the reduction in the ischemia-induced vascular endothelial cell injury through repressing apoptosis and oxidative stress associated with SDX treatment may be due to an increase in GSH synthesis and modulation of the GSH redox system.

Topics: Endothelial Cells; Endothelium; Glucose; Glutathione; Glutathione Disulfide; Glycosaminoglycans; Humans; Ischemia; Oxidation-Reduction; Oxidative Stress; Oxygen

A total of nine patients with diabetes type I and II and with claudications due to macro- and microangiopathies of the lower extremities took sulodexide (Vessel Due F) by the i.m. route for a period of 20 days and then as capsules for 90 days. In all a favourable therapeutic effect was recorded, in particular as regards delay of claudications. The authors recorded lower blood sugar values, lower levels of cholesterol, triglycerides, fibrinogen and plasma viscosity. In the authors' view sulodexide is an important advance in the treatment of diabetics with claudications.

Topics: Arteriosclerosis; Blood Viscosity; Diabetic Angiopathies; Glycosaminoglycans; Humans; Hypolipidemic Agents; Ischemia; Leg; Male; Middle Aged