ArticleBiochemical pharmacology2015
Mechanisms of tolvaptan-induced toxicity in HepG2 cells.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Species, cell proliferation state and oxygen partial pressure are major factors in the in vitro toxicity of repurposed potential ADPKD drugs in human and murine renal proximal tubule cells.Archives of toxicology · 2026Article
- The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Antiproliferative effects of dihydrotanshinone I on autosomal dominant polycystic kidney disease via immunomodulation.The Journal of pharmacology and experimental therapeutics · 2025Article
- 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
- Evaluation of tolvaptan-associated hepatic disorder using different national pharmacovigilance databases.Scientific reports · 2024Article
- The Vasopressin Receptor Antagonist Tolvaptan Counteracts Tumor Growth in a Murine Xenograft Model of Small Cell Lung Cancer.International journal of molecular sciences · 2024Article
- MD simulation-based screening approach identified tolvaptan as a potential inhibitor of Eg5.Molecular diversity · 2023Article
- Hyponatremia and Cancer: From Bedside to Benchside.Cancers · 2023Review
- The VJournal of endocrinological investigation · 2022Article
- Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network.Toxins · 2022Article
- Hepatocrinology.Medical sciences (Basel, Switzerland) · 2021Review
- A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.Nature communications · 2021Article
- Apelin and Vasopressin: The Yin and Yang of Water Balance.Frontiers in endocrinology · 2021Review
- Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning.Journal of endocrinological investigation · 2020Review
- Article
- miR-122 Release in Exosomes Precedes Overt Tolvaptan-Induced Necrosis in a Primary Human Hepatocyte Micropatterned Coculture Model.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- M2 tumor-associated macrophages produce interleukin-17 to suppress oxaliplatin-induced apoptosis in hepatocellular carcinoma.Oncotarget · 2017Article
- Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy for hepatoprotection and diuresis in a rat cirrhotic model.Journal of clinical biochemistry and nutrition · 2017Article
- How impaired efficacy happened between Gancao and Yuanhua: Compounds, targets and pathways.Scientific reports · 2017Article
- Editor's Highlight: Candidate Risk Factors and Mechanisms for Tolvaptan-Induced Liver Injury Are Identified Using a Collaborative Cross Approach.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
Corrections and comments
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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 an increased risk of liver injury. In this study, we explored the underlying mechanisms of hepatotoxicity of tolvaptan using human HepG2 cells. Tolvaptan inhibited cell growth and caused cell death in a concentration- and time-dependent manner. Tolvaptan treatment led to delayed cell cycle progression, accompanied by decreased levels of several cyclins and cyclin-dependent kinases. Tolvaptan was found to cause DNA damage, as assessed by alkaline comet assays; this was confirmed by increased levels of 8-oxoguanine and phosphorylation of histone H2AX. Exposure of HepG2 cells to tolvaptan enhanced cytochrome C release and triggered apoptosis by modulating Bcl-2 family members. The activation of p38 contributed to tolvaptan-mediated apoptosis via down-regulation of Bcl-2. Proteasome inhibition altered tolvaptan-induced cell cycle deregulation and enhanced tolvaptan-induced apoptosis and cytotoxicity. Moreover, tolvaptan treatment induced autophagy. Inhibition of autophagy by knocking-down an autophagy-related gene increased tolvaptan-induced apoptosis and cytotoxicity. Taken together, our findings suggest that the cytotoxicity of tolvaptan results from delayed cell cycle progression, the induction of DNA damage, and the execution of apoptosis. In addition, a number of signaling pathways were perturbed by tolvaptan and played an important role in its cytotoxicity.
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What OpenQuestion holds
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.