Sulodexide suppresses inflammation in human endothelial cells and prevents glucose cytotoxicity

Sulodexide is a mixture of heparin and dermatan sulfate with antithrombotic and profibrynolytic activity. Individual reports suggest the anti-inflammatory action of sulodexin. The goal of this study was to evaluate the effect of sulodexide on the release of the inflammatory mediators from endothelium in normal conditions and in cells chronically exposed to glucose. The experiments were performed on in vitro cultured human umbilical endothelial cells kept for 7 days in standard medium or in the same medium but supplemented with glucose 30 mmol/L. Sulodexide was added to the culture medium in concentrations of 0.125 lipase releasing unit (LRU)/mL, 0.25 LRU/mL, and 0.5 LRU/mL Spontaneous generation of oxygen-derived free radicals and the release of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from the studied cells was evaluated. Additionally, the healing of the injured mesothelium was studied in the presence of sulodexide and glucose. Sulodexide caused the inhibition of the intracellular generation of free radicals in a dose-dependent manner (maximally by 32%, P < 0.01), as well as the inhibition of MCP-1 (maximally by 60%, P < 0.001) and IL-6 (maximally by 69%, P < 0.01). Cells cultured in a medium with glucose 30 mmol/L generated more free radicals (+20%, P < 0.05) and released more MCP-1 (+113%, P < 0.001) and IL-6 (+26%, P < 0.05). Cell monolayers treated with glucose had a decreased ability to heal after mechanical injury (-28%, P < 0.001). All these glucose effects were reversed when cells were exposed to sulodexide simultaneously. The results of our study demonstrate a significant anti-inflammatory action of sulodexide in the endothelial cells and a protective effect of that drug against glucose cytotoxicity.