title: The uremic toxin indoxyl sulfate acts as a pro- or antioxidant on LDL oxidation.
abstract: Uremic toxins have been shown to play a role in chronic kidney disease (CKD) associated oxidative stress. Oxidative stress and inflammation have been associated with increased risk of cardiovascular disease in uraemia. The oxidative modification of LDL may play a role in early atherogenesis. Enhanced LDL oxidation has been found in uremic patients which may account for accelerated atherosclerosis observed in CKD. The uremic toxin indoxyl sulfate (IS) has been reported to exert oxidative and antioxidative activity. Thus, in the present study we have investigated the influence of IS on the atherogenic modifications of LDL exposed in vitro to different oxidising systems. The transition metal ion (Cu(2) ) and hemin/H2O2 induced lipid oxidation reactions monitored by conjugated diene formation, were inhibited by the presence of IS, which points to possible antioxidant effects by this uremic toxin. A protective effect of IS on LDL apoprotein modification by the exposure to the product of the myeloperoxidase/H2O2/Cl(-) system HOCl, was also observed as estimated by protein carbonyl formation. In contrast, a marked increase in conjugated dienes and lipid hydroperoxides was observed when lipid oxidation was initiated by the free radical generator AAPH in presence of IS. The GC-MS analysis revealed the formation of indole-2,3-dione and 6,12-dihydro-6,12-dioxo-indolo[2,1-b]quinazoline (tryptanthrine) in IS/AAPH reaction. A scheme for the generation of tryptanthrine from IS via indoxyl radicals is proposed, which may facilitate LDL lipid oxidation. Our observations add further insight in the Janus-faced properties of this important uremic toxin.
authors.affiliation: Medical University of Vienna (Center of Pathobiochemistry and Genetics), Department of Pathobiochemistry, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Praschberger
authors.affiliation: Medical University of Vienna (Max F. Perutz Laboratories), Department of Medical Biochemistry, Austria.
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
authors.affiliation: Kurt Kitzing GmbH, Wallerstein, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Wanner
authors.affiliation: University of Vienna, Department of Clinical Pharmacy and Diagnostics, Austria.
authors.forename: Leo
authors.initials: L
authors.lastname: Jirovetz
authors.affiliation: Gruppenpraxis Labors.at, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.affiliation: Hospital of the Divine Redeemer, Central Laboratory, Austria.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kapiotis
authors.affiliation: Medical University of Vienna (Center of Pathobiochemistry and Genetics), Department of Pathobiochemistry, Austria.
authors.forename: Bernhard M K
authors.initials: BM
authors.lastname: Gmeiner
authors.affiliation: Medical University of Vienna (Center of Pathobiochemistry and Genetics), Department of Pathobiochemistry, Austria. Electronic address: hildegard.laggner@meduniwien.ac.at.
authors.forename: Hilde
authors.initials: H
authors.lastname: Laggner