| Record Information |
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| Version | 1.0 |
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| Creation date | 2015-10-09 22:30:37 UTC |
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| Update date | 2017-01-19 02:36:23 UTC |
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| FoodComEx ID | PC000422 |
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| FoodDB Record | FDB022179 |
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| Chemical Information |
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| Name | Indoxyl sulfate |
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| Description | Indoxyl sulfate, also known as 3-indoxyl sulfate, is a member of the class of organic compounds known as arylsulfates. These are organic compounds containing a sulfate group that carries an aryl group through an ether group. Indoxyl sulfate is a metabolite of the common amino acid tryptophan and is derived through the consumption, digestion and microbial processing of protein-rich foods. Indoxyl sulfate is technically a bacterial co-metabolite, meaning that it is derived from both bacterial and host metabolism. Specifically, it is generated from dietary L-tryptophan which is converted to indole in the large intestine via tryptophanase-expressing gastrointestinal bacteria (PMID: 27102537). The resulting indole is converted to indoxyl in the liver via enzyme-mediated hydroxylation by the CYP450 enzyme CYP2E1 (PMID 11808865). Subsequently, indoxyl is converted into indoxyl sulfate by the SULT1A1 sulfotransferase enzyme in the liver (PMID: 12064372). Indoxyl sulfate has been identified as a uremic toxin according to the European Uremic Toxin Working Group (PMID: 22626821 ) and is classified as a protein-bound uremic solute. Indoxyl sulfate is known to bind to serum albumin (PMID: 22626821), to be transported by the OAT1 transporter (PMID: 34678967) and to be an agonist for the arylhydrocarbon receptor (AhR) (PMID: 32527975). High concentrations of indoxyl sulfate in whole blood or blood plasma are known to be associated with the development and progression of chronic kidney disease (CKD) as well as the development of cardiovascular disease (CVD) in humans and other mammals (PMID: 28754616). As a uremic toxin, indoxyl sulfate is known to stimulate glomerular sclerosis (PMID: 8035108), interstitial fibrosis (PMID: 33138205) and increase the rate of progression of renal failure. Indoxyl sulfate is a known tubular toxin (i.e., a renal tubule toxin) and directly induces apoptotic and necrotic cell death of tubular cells in the kidney (PMID: 33138205). Indoxyl sulfate upregulates signal transducers and activators of transcription 3 phosphorylation leading to increases in TGF-β1, monocyte chemotactic protein-1 and alpha-smooth muscle actin production, all of which participate in interstitial inflammation, renal fibrosis and, consequently, CKD progression (PMID: 33138205). Indoxyl sulfate is also a known cardiotoxin (PMID: 30200452). In plasma, indoxyl sulfate induces endothelial dysfunction by inhibiting endothelial proliferation and migration as well as disrupting wound repair in vitro (PMID: 14717914). Indoxyl sulfate is known to impair angiogenesis by suppressing endothelial cell tube formation and endothelial cell proliferation via chronic aryl hydrocarbon receptor (AhR) activation. Many studies suggest that indoxyl sulfate increases oxidative stress which further exacerbates endothelial dysfunction (PMID: 20876676). This ultimately leads to atherosclerosis, peripheral artery disease and cardiovascular disease, which are common in patients with CKD (PMID: 33456671). In hemodialyzed patients, serum levels of indoxyl sulfate are associated with levels of pentosidine, a marker of carbonyl and oxidative stress (PMID: 14524578). In vitro, indoxyl sulfate increases reactive oxygen species (ROS) production in tubular cells and increases NAD(P)H oxidase activity in endothelial cells (PMID: 29976888). Indoxyl sulfate also strongly decreases the levels of glutathione, one of the most active antioxidant systems of the cell (PMID: 29474405). In addition to its well-known renal toxicity and cardiotoxicity, indoxyl sulfate appears to have osteotoxic, myotoxic and neurotoxic effects. As an osteotoxin, indoxyl sulfate impairs osteoblast function and induces abnormalities of bone turnover (PMID: 28781957). Indoxyl sulfate appears to induce low-turnover bone disease by directly acting on both osteoblasts and osteoclast precursors to suppress bone formation and bone resorption. In vitro studies with mouse osteoblasts have shown that indoxyl sulfate suppresses the gene expression of osterix, osteocalcin, and bone morphogenetic protein 2 (BMP2), thereby inhibiting the formation of mineralized bone nodules, leading to suppressed bone formation (PMID: 28781957). As a myotoxin, indoxyl sulfate appears to induce sarcopenia, which is especially common in patients with CKD. In particular, indoxyl sulfate increases the production of several factors related to skeletal muscle breakdown, including reactive oxygen species (ROS) and inflammatory cytokines (TNF-α, IL-6 and TGF-β1) (PMID: 27549031). It also enhances the production of muscle atrophy-related genes, myostatin and atrogin-1 (PMID: 27549031). As a neurotoxin, indoxyl sulfate appears to disrupt the blood brain barrier. In particular, indoxyl sulfate binds to the aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system. The binding of indoxyl sulfate to the AhR leads to blood-brain barrier disruption, which is associated with cognitive impairment in animal models of CKD (PMID: 32527975). Indoxyl sulfate, along with quinolinic acid and kynurenine, are significantly elevated in blood/plasma of individuals with dementia (PMID: 34493657). Recently, indoxyl sulfate has been shown to be associated with altered neural processing (as shown by functional MRI) and the serum abundance of indoxyl sulfate is positively correlated with severity of psychic anxiety in humans (PMID: 34697401). |
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| CAS Number | 487-94-5 |
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| Structure | |
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| Synonyms | | Synonym | Source |
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| 1H-indol-3-yl Hydrogen sulfate | HMDB | | 1H-indol-3-yl Hydrogen sulphate | HMDB | | 3-Indolyl hydrogen sulfate | ChEBI | | 3-Indolyl hydrogen sulfuric acid | Generator | | 3-Indolyl hydrogen sulphate | Generator | | 3-Indolyl hydrogen sulphuric acid | Generator | | 3-Indolyl sulfate | ChEBI | | 3-Indolyl sulfuric acid | Generator | | 3-Indolyl sulphate | Generator | | 3-Indolyl sulphuric acid | Generator | | 3-Indoxyl sulfate | ChEBI | | 3-Indoxyl sulfuric acid | Generator | | 3-Indoxyl sulphate | Generator | | 3-Indoxyl sulphuric acid | Generator | | 3-Indoxylsulfate | Generator | | 3-Indoxylsulfuric acid | hmdb | | 3-Indoxylsulphate | Generator | | 3-Indoxylsulphuric acid | Generator | | Indican | hmdb | | Indol-3-ol | hmdb | | indol-3-yl Hydrogen sulfate | ChEBI | | indol-3-yl Hydrogen sulfuric acid | Generator | | indol-3-yl Hydrogen sulphate | Generator | | indol-3-yl Hydrogen sulphuric acid | Generator | | Indol-3-yl sulfate | hmdb | | indol-3-yl Sulfuric acid | Generator | | indol-3-yl sulphate | hmdb | | indol-3-yl Sulphuric acid | Generator | | Indoxyl sulfic acid | hmdb | | Indoxyl sulfuric acid | Generator | | Indoxyl sulphate | ChEBI | | Indoxyl sulphuric acid | Generator | | Indoxylsulfate | Generator | | Indoxylsulfuric acid | ChEBI | | Indoxylsulphate | Generator | | Indoxylsulphuric acid | Generator |
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| Chemical Formula | C8H7NO4S |
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| IUPAC name | (1H-indol-3-yl)oxidanesulfonic acid |
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| InChI Identifier | InChI=1S/C8H7NO4S/c10-14(11,12)13-8-5-9-7-4-2-1-3-6(7)8/h1-5,9H,(H,10,11,12) |
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| InChI Key | BXFFHSIDQOFMLE-UHFFFAOYSA-N |
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| Isomeric SMILES | OS(=O)(=O)OC1=CNC2=CC=CC=C12 |
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| Average Molecular Weight | 213.21 |
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| Monoisotopic Molecular Weight | 213.009578407 |
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| Chemical Taxonomy |
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| Description | Belongs to the class of organic compounds known as arylsulfates. These are organic compounds containing a sulfate group that carries an aryl group through an ether group. |
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| Kingdom | Organic compounds |
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| Super Class | Organic acids and derivatives |
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| Class | Organic sulfuric acids and derivatives |
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| Sub Class | Arylsulfates |
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| Direct Parent | Arylsulfates |
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| Alternative Parents | |
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| Substituents | - Arylsulfate
- Indole
- Indole or derivatives
- Substituted pyrrole
- Sulfuric acid monoester
- Sulfate-ester
- Sulfuric acid ester
- Benzenoid
- Pyrrole
- Heteroaromatic compound
- Organoheterocyclic compound
- Azacycle
- Organooxygen compound
- Organonitrogen compound
- Organic oxygen compound
- Organic nitrogen compound
- Hydrocarbon derivative
- Organopnictogen compound
- Organic oxide
- Aromatic heteropolycyclic compound
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| Molecular Framework | Aromatic heteropolycyclic compounds |
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| External Descriptors | |
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| Physico-Chemical Properties - Experimental |
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| Property | Value | Reference |
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| Experimental logP | Not Available | |
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| Experimental Water Solubility | Not Available | |
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| Melting Point | Not Available | |
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| Foods of Origin |
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| Food | Content Range | Average | Reference |
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| Food | | | Reference |
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| Production Data |
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| Production Method | commercial |
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| Production Method Reference | Not Available |
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| Production Method Reference File | Not Available |
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| Quantity Available | Production upon request, up to 70 mg |
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| Delivery Time | Not Available |
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| Storage Form | solid |
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| Storage Conditions | -80°C |
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| Stability | Not Available |
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| Purity | Not Available |
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| Spectra |
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| Spectral Data Upon Request | Not Available |
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| Provider Information |
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| Commercial Vendors |
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| Not Available |
