ArticleRedox biology2015
Epalrestat increases glutathione, thioredoxin, and heme oxygenase-1 by stimulating Nrf2 pathway in endothelial cells.
Article in Redox biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- A Chilean Berry Concentrate Protects against Postprandial Oxidative Stress and Increases Plasma Antioxidant Activity in Healthy Humans.Oxidative medicine and cellular longevity · 2017Trial
- Targeting Oxidative Stress and Mitochondrial Dysfunction in Diabetic Neuropathy: Mechanisms and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2026Review
- Repurposing of epalrestat for neuroprotection in parkinson's disease via activation of the KEAP1/Nrf2 pathway.Journal of neuroinflammation · 2025Article
- Cognition enhancing abilities of vitamin D, epalrestat and their combination in diabetic rats with and without scopolamine induced amnesia.Cognitive neurodynamics · 2022Article
- Fermented Oyster Extract Attenuated Dexamethasone-Induced Muscle Atrophy by Decreasing Oxidative Stress.Molecules (Basel, Switzerland) · 2021Article
- Neuroprotective Effect of Epalrestat on Hydrogen Peroxide-Induced Neurodegeneration in SH-SY5Y Cellular Model.Journal of microbiology and biotechnology · 2021Article
- Epalrestat suppresses cadmium-induced cytotoxicity through Nrf2 in endothelial cells.Experimental and therapeutic medicine · 2021Article
- Atypical Antipsychotic Drug Ziprasidone Protects against Rotenone-Induced Neurotoxicity: An In Vitro Study.Molecules (Basel, Switzerland) · 2020Article
- The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer.Molecular biology reports · 2020Article
- WJ-39, an Aldose Reductase Inhibitor, Ameliorates Renal Lesions in Diabetic Nephropathy by Activating Nrf2 Signaling.Oxidative medicine and cellular longevity · 2020Article
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG.Disease models & mechanisms · 2019Article
- Glutathione Induced Immune-Stimulatory Activity by Promoting M1-Like Macrophages Polarization via Potential ROS Scavenging Capacity.Antioxidants (Basel, Switzerland) · 2019Article
- Effects of JUN and NFE2L2 knockdown on oxidative status and NFE2L2/AP-1 targets expression in HeLa cells in basal conditions and upon sub-lethal hydrogen peroxide treatment.Molecular biology reports · 2019Article
- Activation of Nrf2 signaling by natural products-can it alleviate diabetes?Biotechnology advances · 2018Review
- Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Ameliorative potential of rutin in combination with nimesulide in STZ model of diabetic neuropathy: targeting Nrf2/HO-1/NF-kB and COX signalling pathway.Inflammopharmacology · 2018Article
- Efficacy and Safety of the Injection of the Traditional Chinese Medicine Puerarin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis of 53 Randomized Controlled Trials.Evidence-based complementary and alternative medicine : eCAM · 2018Review
- Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice.Journal of clinical biochemistry and nutrition · 2017Article
- Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway.Molecules (Basel, Switzerland) · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epalrestat (EPS) is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Recently, we found that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH) in rat Schwann cells. GSH plays a crucial role in protecting endothelial cells from oxidative stress, thereby preventing vascular diseases. Here we show that EPS increases GSH levels in not only Schwann cells but also endothelial cells. Treatment of bovine aortic endothelial cells (BAECs), an in vitro model of the vascular endothelium, with EPS caused a dramatic increase in intracellular GSH levels. This was concomitant with the up-regulation of glutamate cysteine ligase, an enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Moreover, EPS stimulated the expression of thioredoxin and heme oxygenase-1, which have important redox regulatory functions in endothelial cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates the expression of antioxidant genes. EPS increased nuclear Nrf2 levels in BAECs. Nrf2 knockdown by siRNA suppressed the EPS-induced glutamate cysteine ligase, thioredoxin-1, and heme oxygenase-1 expression. Interestingly, LY294002, an inhibitor of phosphatidylinositol 3-kinase, abolished the EPS-stimulated GSH synthesis, suggesting that the kinase is associated with Nrf2 activation induced by EPS. Furthermore, EPS reduced the cytotoxicity induced by H2O2 and tert-butylhydroperoxide, indicating that EPS plays a role in protecting cells from oxidative stress. Taken together, the results provide evidence that EPS exerts new beneficial effects on endothelial cells by increasing GSH, thioredoxin, and heme oxygenase-1 levels through the activation of Nrf2. We suggest that EPS has the potential to prevent several vascular diseases caused by oxidative stress.
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