ArticleRedox biology2013
Epalrestat increases intracellular glutathione levels in Schwann cells through transcription regulation.
Article in Redox biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting Oxidative Stress and Mitochondrial Dysfunction in Diabetic Neuropathy: Mechanisms and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2026Review
- Cognition enhancing abilities of vitamin D, epalrestat and their combination in diabetic rats with and without scopolamine induced amnesia.Cognitive neurodynamics · 2022Article
- Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.Annals of neurology · 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
- Epalrestat improves motor symptoms by reducing oxidative stress and inflammation in the reserpine induced mouse model of Parkinson's disease.Animal models and experimental medicine · 2020Article
- Targeting the Nrf2/ARE Signalling Pathway to Mitigate Isoproterenol-Induced Cardiac Hypertrophy: Plausible Role of Hesperetin in Redox Homeostasis.Oxidative medicine and cellular longevity · 2020Article
- Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS.Journal of pharmaceutical analysis · 2019Article
- General toxicity assessment of the novel aldose reductase inhibitor cemtirestat.Interdisciplinary toxicology · 2019Article
- Activation of Nrf2 signaling by natural products-can it alleviate diabetes?Biotechnology advances · 2018Review
- Efficacy of epalrestat plus α-lipoic acid combination therapyNeural regeneration research · 2018Article
- Epalrestat Stimulated Oxidative Stress, Inflammation, and Fibrogenesis in Mouse Liver.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Hepatoprotective effects of rice-derived peptides against acetaminophen-induced damage in mice.Journal of clinical biochemistry and nutrition · 2017Article
- Nerves Control Redox Levels in Mature Tissues Through Schwann Cells and Hedgehog Signaling.Antioxidants & redox signaling · 2016Article
- Amelioration of Bleomycin-induced Pulmonary Fibrosis of Rats by an Aldose Reductase Inhibitor, Epalrestat.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2015Article
- Epalrestat increases glutathione, thioredoxin, and heme oxygenase-1 by stimulating Nrf2 pathway in endothelial cells.Redox biology · 2015Article
- Hydrogen exerts neuroprotective effects by inhibiting oxidative stress in experimental diabetic peripheral neuropathy rats.Medical gas researchArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epalrestat (EPS), approved in Japan, is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Here we report that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH), which is important for protection against oxidative injury, through transcription regulation. Treatment of Schwann cells with EPS caused a dramatic increase in intracellular GSH levels. EPS increased the mRNA levels of γ-glutamylcysteine synthetase (γ-GCS), the enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a central role in regulating the expression of γ-GCS. ELISA revealed that EPS increased nuclear Nrf2 levels. Knockdown of Nrf2 by siRNA suppressed the EPS-induced GSH biosynthesis. Furthermore, pretreatment with EPS reduced the cytotoxicity induced by H2O2, tert-butylhydroperoxide, 2,2'-azobis (2-amidinopropane) dihydrochloride, and menadione, indicating that EPS plays a role in protecting against oxidative stress. This is the first study to show that EPS induces GSH biosynthesis via the activation of Nrf2. We suggest that EPS has new beneficial properties that may prevent the development and progression of disorders caused by oxidative stress.
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