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Indoxyl sulfate-d5 is intended for use as an internal standard for the quantification of indoxyl sulfate by GC- or LC-MS. Indoxyl sulfate is a uremic toxin and a metabolite of tryptophan .1 It is formed via sulfation of indole, an intermediate generated from tryptophan by intestinal bacteria, by the sulfotransferase (SULT) isoform 1A1 variant 2 (SULT1A1*2) in the liver.2,1 Indoxyl sulfate activates the aryl hydrocarbon receptor (AhR) in HepG2 40/6 hepatoma cells (EC50 = 12.1 nM in a reporter assay).3 It also inhibits the organic anion transporter (OAT) isoforms OAT1 and OAT3 (Kis = 34.2 and 74.4 µM, respectively for the rat transporters) in S2 proximal tubule cells.4 Indoxyl sulfate (0.2 and 1 mM) increases superoxide anion and nitric oxide levels in isolated human mononuclear blood cells.5 It increases serum creatinine and blood urea nitrogen (BUN) levels in the 5/6 nephrectomized rat model of chronic renal failure when administered at a dose of 50 mg/kg.4

1.Niwa, T.Uremic toxicity of indoxyl sulfateNagoya J. Med. Sci.72(1-2)1-11(2010) 2.Banoglu, E., and King, R.S.Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfateEur. J. Drug Metab. Pharmacokinet.27(2)135-140(2002) 3.Schroeder, J.C., Dinatale, B.C., Murray, I.A., et al.The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptorBiochemistry49(2)393-400(2010) 4.Enomoto, A., Takeda, M., Tojo, A., et al.Role of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxicityJ. AM. Soc. Nephrol.13(7)1711-1720(2002) 5.Pieniazek, A., Gwozdzinski, L., Hikisz, P., et al.Indoxyl sulfate generates free radicals, decreases antioxidant defense, and leads to damage to mononuclear blood cellsChem. Res. Toxicol.31(9)869-875(2018).

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