New insight into the redox properties of uremic solute indoxyl sulfate as a pro- and anti-oxidant.
ABSTRACT 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.
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ABSTRACT: The uremic syndrome is attributed to the progressive retention of a large number of compounds which, under normal conditions, are excreted by healthy kidneys. The compounds are called uremic toxins when they interact negatively with biological functions. The present review focuses on a specific class of molecules, namely the family of protein-bound uremic toxins. Recent experimental studies have shown that protein-bound toxins are involved not only in the progression of chronic kidney disease (CKD), but also in the generation and aggravation of cardiovascular disease. Two protein-bound uremic retention solutes, namely indoxyl sulfate and p-cresyl sulfate, have been shown to play a prominent role. However, although these two molecules belong to the same class of molecules, exert toxic effects on the cardiovascular system in experimental animals, and accumulate in the serum of patients with CKD they may have different clinical impacts in terms of cardiovascular disease and other complications. The principal aim of this review is to evaluate the effect of p-cresyl sulfate and indoxyl sulfate retention on CKD patient outcomes, based on recent clinical studies.Toxins. 07/2011; 3(7):911-9.