Phenyl sulfate, indoxyl sulfate and p-cresyl sulfate decrease glutathione level to render cells vulnerable to oxidative stress in renal tubular cells

PloS One
Takeo EdamatsuYoshiharu Itoh

Abstract

In chronic kidney disease patients, oxidative stress is generally associated with disease progression and pathogenesis of its comorbidities. Phenyl sulfate is a protein-bound uremic solute, which accumulates in chronic kidney disease patients, but little is known about its nature. Although many reports revealed that protein-bound uremic solutes induce reactive oxygen species production, the effects of these solutes on anti-oxidant level have not been well studied. Therefore, we examined the effects of protein-bound uremic solutes on glutathione levels. As a result, indoxyl sulfate, phenyl sulfate, and p-cresyl sulfate decreased glutathione levels in porcine renal tubular cells. Next we examined whether phenyl sulfate-treated cells becomes vulnerable to oxidative stress. In phenyl sulfate-treated cells, hydrogen peroxide induced higher rates of cell death than in control cells. Buthionine sulfoximine, which is known to decrease glutathione level, well mimicked the effect of phenyl sulfate. Finally, we evaluated a mixture of indoxyl sulfate, phenyl sulfate, and p-cresyl sulfate at concentrations comparable to the serum concentrations of hemodialysis patients, and we confirmed its decreasing effect on glutathione level. In conclus...Continue Reading

Citations

Jun 15, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kiyotaka UchiyamaHiroshi Itoh
Apr 25, 2019·Nature Communications·Koichi KikuchiTakaaki Abe
May 22, 2019·Metabolomics : Official Journal of the Metabolomic Society·Mai YamamotoPhilip Britz-McKibbin
Oct 2, 2020·Analytical Methods : Advancing Methods and Applications·Wen LiuTong Tong Wang
Dec 15, 2020·Chemico-biological Interactions·Hamit Hakan Armağan, Mustafa Nazıroğlu
Jan 19, 2021·Oxidative Medicine and Cellular Longevity·Iwona KwiatkowskaDariusz Pawlak
May 1, 2021·Nutrients·Chiara FaveroMaria Dolores Sanchez-Niño
May 20, 2021·Antioxidants & Redox Signaling·Thomas EbertPaul G Shiels
Jul 3, 2021·Antioxidants·Chien-Lin LuMing-Chieh Ma
Jul 3, 2021·International Journal of Molecular Sciences·Anna PieniazekLukasz Gwozdzinski

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