ArticleScientific reports2019
Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The Role of Immune Cells as Modulators of Progression in Polycystic Kidney Disease: A Systematic Review.Kidney360 · 2026Pooled it
- Heparin-binding protein aggravates sepsis-induced acute lung injury by inhibiting the PERK-Nrf2-HO-1 signaling pathway.Journal of molecular histology · 2026Article
- Renoprotective Effects of MIT-001 in Ischemia-Reperfusion Injury: Modulation of Ferroptosis, ROS and Fibrotic Markers.Journal of cellular and molecular medicine · 2025Article
- [Research progress of tolvaptan in the treatment of refractory ascites in cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway.Open life sciences · 2025Article
- Reactive Oxygen Species in Cystic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells.Natural products and bioprospecting · 2024Article
- Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.Biomolecules & therapeutics · 2024Review
- Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells.Oncology reports · 2024Article
- NRF2 in kidney physiology and disease.Physiological reports · 2024Review
- Propofol Pretreatment Inhibits Liver Damage in Mice with Hepatic Ischemia/Reperfusion Injury and Protects Human Hepatocyte in Hypoxia/Reoxygenation.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Salidroside alleviates diet-induced obesity and insulin resistance by activating Nrf2/ARE pathway and enhancing the thermogenesis of adipose tissues.Food science & nutrition · 2023Article
- Exercise-induced myocardial hypertrophy preconditioning promotes fibroblast senescence and improves myocardial fibrosis through Nrf2 signaling pathway.Cell cycle (Georgetown, Tex.) · 2023Article
- Gelsemine Exerts Neuroprotective Effects on Neonatal Mice with Hypoxic-Ischemic Brain Injury by Suppressing Inflammation and Oxidative Stress via Nrf2/HO-1 Pathway.Neurochemical research · 2023Article
- Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases.International journal of molecular sciences · 2023Review
- Astragaloside IV alleviates 1-deoxysphinganine-induced mitochondrial dysfunction during the progression of chronic kidney disease through p62-Nrf2 antioxidant pathway.Frontiers in pharmacology · 2023Article
- Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls.Antioxidants (Basel, Switzerland) · 2022Review
- Current Hydration Habits: The Disregarded Factor for the Development of Renal and Cardiometabolic Diseases.Nutrients · 2022Review
- ER Stress in COVID-19 and Parkinson's Disease: In Vitro and In Silico Evidences.Brain sciences · 2022Article
- Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach.Journal of clinical medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tolvaptan, a vasopressin type 2 receptor antagonist initially developed to increase free-water diuresis, has been approved for the treatment of autosomal dominant polycystic kidney disease in multiple countries. Furthermore, tolvaptan has been shown to improve the renal functions in rodent models of chronic kidney disease (CKD); however, the underlying molecular mechanisms remain unknown. CKD is characterized by increased levels of oxidative stress, and an antioxidant transcription factor-nuclear factor erythroid 2-related factor 2 (Nrf2)-has been gaining attention as a therapeutic target. Therefore, we investigated the effects of tolvaptan and a well-known Nrf2 activator, bardoxolone methyl (BARD) on Nrf2. To determine the role of tolvaptan, we used a renal cortical collecting duct (mpkCCD) cell line and mouse kidneys. Tolvaptan activated Nrf2 and increased mRNA and protein expression of antioxidant enzyme heme oxygenase-1 (HO-1) in mpkCCD cells and the outer medulla of mouse kidneys. In contrast to BARD, tolvaptan regulated the antioxidant systems via a unique mechanism. Tolvaptan activated the Nrf2/HO-1 antioxidant pathway through phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK). As a result, tolvaptan and BARD could successfully generate synergistic activating effects on Nrf2/HO-1 antioxidant pathway, suggesting that this combination therapy can contribute to the treatment of CKD.
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