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Indoxyl sulfate (IS) is a uremic toxin that has been associated with inflammation, oxidative stress as well as with the progression of chronic kidney disease (CKD). Indoxyl sulfate is a protein metabolite that is concentrated in the serum of CKD patients. IS is a well-known uremic toxin but there are very few reports on the effect of IS on cells including mononuclear cells (MNCs). We hypothesized that a high concentration of IS in CKD patients may induce changes in redox balance in the in vitro cells exposed. In the present study, we investigated the effect of indoxyl sulfate on free radical production, antioxidant capacity and protein damage in the mononuclear blood cells. As already determined, the concentrations (0.2 or 1 mM) of IS used in this study do not affect the survival rate of MNCs. For both the concentrations of indoxyl sulfate, there was an increase in superoxide and nitric oxide, and a release of other reactive oxygen species (ROS) inside the cells, as measured using fluorescent probes. However, an increase in other ROS as indicated by H2DCF-DA was found only for 1 mM of IS. Moreover, a decrease in the non-enzymatic antioxidant capacity (NAC) and an increase in the superoxide dismutase activity after incubation of the cells with indoxyl sulfate were observed. Furthermore, we found an increase in the levels of carbonyl compounds and peroxides in the cells treated with both the concentrations of IS. The obtained results show that indoxyl sulfate induces oxidative stress and a decrease in antioxidant defense in cells leading to lipids and proteins damage.
This article was published in the following journal.
Name: Chemical research in toxicology
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Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.
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An enzyme that catalyzes the activation of sulfate ions by ATP to form adenosine-5'-phosphosulfate and pyrophosphate. This reaction constitutes the first enzymatic step in sulfate utilization following the uptake of sulfate. EC 18.104.22.168.
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