New insight into the redox properties of uremic solute indoxyl sulfate as a pro- and anti-oxidant.

Indoxyl sulfate, an extensively investigated uremic toxin, is involved in the progression of chronic kidney disease (CKD). Recent clinical data indicate that serum levels of indoxyl sulfate are a powerful predictor of overall and cardiovascular mortality. Under CKD conditions, indoxyl sulfate induces oxidative stress, which involves the production of excessive levels of reactive oxygen species in renal tubular cells, mesangial cells, vascular endothelial cells, and osteoblast cells. In contrast, our recent findings explain, at least in part, the role that indoxyl sulfate plays in protecting against oxidative stress under normal-physiological conditions. Namely, under CKD conditions, the pro-oxidant properties of indoxyl sulfate exceed its anti-oxidant properties. These findings provide new insights into the dual role of indoxyl sulfate, which appears to be concentration-dependent, with respect to its pro- or anti-oxidative properties.