Phenyl sulfate

Phenyl sulfate is a protein-bound uremic solute [1].

Phenyl sulfate is one of the protein-bound uremic solutes which have been reported to induce reactive oxygen species production and decrease glutathione levels, rendering the cells vulnerable to oxidative stress. Phenyl sulfate accumulates in chronic kidney disease patients, and was proposed as a novel biomarker for the effect of AST-120, an orally administered spherical carbon adsorbent that can adsorb various small molecule uremic toxins [1].

In porcine renal tubular cells, phenyl sulfate (0, 0.2, 0.5, 2, 5, 10 mmol/L) decreased glutathione levels in a dose-dependent manner. In 0.5, 2, 5, or 10 mmol/L phenyl sulfate-treated cells, 20 μmol/L of hydrogen peroxide decreased cellular viability by 76%, 81%, 89%, and 94%, respectively, whilst in control cells, the same concentration of hydrogen peroxide only decreased cellular viability by 62%. These differences between control cells and phenyl sulfate-treated cells were statistically significant [1].

In KKAy mice fed on a high-fat diet (HFD), oral administration of 50 mg/kg phenyl sulfate for 6 weeks increased albuminuria. Electron micrographs revealed podocyte effacement, as well as glomerular basement membrane thickening and damage in the PS-treated HFD-KKAy kidney [2].  

References:

[1]. Edamatsu T, Fujieda A, Itoh Y. Phenyl sulfate, indoxyl sulfate and p-cresyl sulfate decrease glutathione level to render cells vulnerable to oxidative stress in renal tubular cells. PLoS One, 2018, 13(2): e0193342.

[2]. Kikuchi K, Saigusa D, Kanemitsu Y, et al. Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Nature Communications, 2019, 10(1): 1835.