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Indoxyl sulfate, also known as 3-indoxylsulfate and 3-indoxylsulfuric acid, is a metabolite of dietary that acts as a cardiotoxin and uremic toxin. High concentrations of indoxyl sulfate in blood plasma are known to be associated with the development and progression of chronic kidney disease and vascular disease in humans. As a uremic toxin, it stimulates glomerular sclerosis and renal interstitial fibrosis.
Indole is produced from in the human intestine via tryptophanase-expressing Gut flora. Indoxyl is produced from indole via enzyme-mediated hydroxylation in the liver; in vitro experiments with rat and human microsome suggest that the CYP450 enzyme CYP2E1 hydroxylates indole into indoxyl. Subsequently, indoxyl is converted into indoxyl sulfate by sulfotransferase in the liver; based upon in vitro experiments with recombinant human sulfotransferases, SULT1A1 appears to be the primary sulfotransferase enzyme involved in the conversion of indoxyl into indoxyl sulfate.
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