Drug induced endothelial dysfunction: functional role of oxidative stress

Abstract

Reactive oxygen species (ROS) are increasingly recognised as a major cause for altering normal endothelial cell functions. Several studies have revealed that pharmacological agents in the treatment of various diseases can increase ROS load in the body and result in endothelial dysfunction. Anti cancer drugs, immunosuppressive drugs, anti-retroviral drugs, aldosterone and aldosterone antagonists, diethyldithiocarbamate, nanoparticle drugs and drug carriers have been found to cause endothelial dysfunction through oxidative stress. ROS mediated endothelial dysfunction can adversely affect bioavailability of nitric oxide, endothelium-dependent vasodilatation, cell permeability, endothelial cell growth and survival. Whether anti oxidant therapies would really be beneficial to prevent the endothelial oxidative stress associated drugs is unclear. Redox biology of drug induced endothelial dysfunction involves highly complex pathways. Understanding mechanisms of regulated generation of ROS in endothelial cells and downstream effects are necessary to design appropriate therapeutic measures. The functional role of ROS in drug induced endothelial dysfunction and currently known mechanisms are reviewed in this article.