Androgenic Anabolic Steroids Cause Thiol Imbalance in the Vascular Endothelial Cells

Androgenic anabolic steroids (AASs) are synthetic drugs structurally related to testosterone, with the ability to bind to androgen receptors. Their uncontrolled use by professional and recreational sportspeople is a widespread problem. AAS abuse is correlated with severe damage to the cardiovascular system, including changes in homeostasis and coagulation disorders. AASs alter vascular function by blocking nitric oxide (NO)-mediated dilation, impairing endothelial growth and by potentiating vasoconstrictor signals.

This paper demonstrated that long-term use of AASs (nandrolone and boldenone), negatively affects the basic cell functions of vascular endothelial cells. The susceptibility of endothelial cells to AASs depends on the expression of androgen receptors, although cells without androgen receptors can also be affected by high doses of AASs to a limited extent. Seven-day incubation with AASs diminishes endothelial cell proliferation and migration (determined by transwell and scratch migration assay) and monolayer formation (using transendothelial electrical resistance assay).

Disturbances in cell function were accompanied by downregulation of peroxiredoxins (PRDX1 and PRDX2), involved in maintaining the thiol-disulphide balance. In addition, AASs increased oxidation of the non-enzymatic thiol buffer, glutathione (GSH), reduced secretion of thiol oxidoreductase protein disulphide isomerase (PDI) from endothelial cells and affected the thiol pattern of PDI.

These changes may be related to a thiol-disulfide imbalance and vascular endothelium dysfunction, that are often correlated with abnormal platelet aggregation, inflammation, increased vascular permeability, and vascular smooth muscle cell proliferation-all of which are observed in athletes who abuse AASs.