Rosiglitazone attenuates indoxyl sulphate-induced endothelial dysfunction

Indoxyl sulphate is a protein-bound uraemic toxin that has deleterious effects on the cardiovascular system. Rosiglitazone (RGZ) is an insulin sensitizer used for glycaemic control in type 2 diabetes. Rosiglitazone has been shown to be beneficial for cardiovascular disease because of its pleiotropic effects. Whether RGZ can improve indoxyl sulphate-induced endothelial damage has not been investigated. In the present in vitro study, we examined the effects of RGZ on indoxyl sulphate-induced endothelial injury. Endothelial cells were exposed to RGZ (5 and 10mol/L) and then treated with indoxyl sulphate (100 and 1000mol/L) for 48h. Indoxyl sulphate upregulated intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 expression. Indoxyl sulphate also increased the abundance of NADPH oxidase 4 (NOX4) and nuclear factor (NF)-B. Both extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) signalling pathways were activated after 48h treatment with indoxyl sulphate. Pretreatment of cells with both concentrations of RGZ improved indices of endothelial injury. In addition, RGZ attenuated the increase in NOX4 and NF-B and prevented the activation of the ERK1/2 and p38 MAPK signalling pathways. We conclude that RGZ ameliorates indoxyl sulphate-induced endothelial injury.