ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Human Sulfotransferases Enhance the Cytotoxicity of Tolvaptan.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.Expert opinion on drug metabolism & toxicology · 2025Review
- Tolvaptan safety in autosomal-dominant polycystic kidney disease; a focus on idiosyncratic drug-induced liver injury liabilities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Identification and Characterization of Two Aryl Sulfotransferases from Deep-Sea Marine Fungi and Their Implications in the Sulfation of Secondary Metabolites.Marine drugs · 2024Article
- Sulphotransferase-mediated toxification of chemicals in mouse models: effect of knockout or humanisation of SULT genes.Essays in biochemistry · 2024Review
- MD simulation-based screening approach identified tolvaptan as a potential inhibitor of Eg5.Molecular diversity · 2023Article
- The Role of Sulfotransferases in Liver Diseases.Drug metabolism and disposition: the biological fate of chemicals · 2020Review
- Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1.Acta pharmaceutica Sinica. B · 2018Article
- Effects of human sulfotransferases on the cytotoxicity of 12-hydroxynevirapine.Biochemical pharmacology · 2018Article
- Transcriptional Regulation of Human Cytosolic Sulfotransferase 1C3 by Peroxisome Proliferator-Activated Receptor γ in LS180 Human Colorectal Adenocarcinoma Cells.Molecular pharmacology · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tolvaptan, a vasopressin receptor 2 antagonist used to treat hyponatremia, has recently been reported to be associated with liver injury. Sulfotransferases (SULTs) have been implicated as important detoxifying and/or activating enzymes for numerous xenobiotics, drugs, and endogenous compounds. To characterize better the role of SULTs in tolvaptan metabolism, HEK293 cells stably overexpressing 12 human SULTs were generated. Using these cell lines, the extent of tolvaptan sulfate formation was assessed by reversed-phase high-performance liquid chromatography through comparison to a synthetic standard. Of the 12 known human SULTs, no detectable sulfation of tolvaptan was observed with SULT1A1, SULT1A2, SULT1A3, SULT1C2, SULT1C4, SULT4A1, or SULT6B1. The affinity of individual SULT isozymes, as determined by Km analysis, was SULT1C3 >> SULT2A1 > SULT2B1 ∼ SULT1B1 > SULT1E1. The half inhibitory concentration of tolvaptan on cell growth in HEK293/SULT1C3 cells and HEK293/CYP3A4 & SULT1C3 cells was significantly lower than that in the corresponding HEK293/vector cells or HEK293/CYP3A4 & SULT vector cells. Moreover, exposing cells to tolvaptan in the presence of cyclosporine A, an inhibitor of the drug efflux transporters, significantly increased the intracellular levels of tolvaptan sulfate and decreased the cell viability in HEK293/SULT1C3 cells. These data indicate that sulfation increased the cytotoxicity of tolvaptan.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.