ArticlePloS one2013
A new approach to control the enigmatic activity of aldose reductase.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- An Investigation of 5-HalogenatedMedicines (Basel, Switzerland) · 2025Article
- Epalrestat Alleviates Reactive Oxygen Species and Endoplasmic Reticulum Stress by Maintaining Glycosylation in IMS32 Schwann Cells Under Exposure to Galactosemic Conditions.International journal of molecular sciences · 2025Article
- The Role of Aldose Reductase in Polyol Pathway: An Emerging Pharmacological Target in Diabetic Complications and Associated Morbidities.Current pharmaceutical biotechnology · 2024Review
- Response of a Human Lens Epithelial Cell Line to Hyperglycemic and Oxidative Stress: The Role of Aldose Reductase.Antioxidants (Basel, Switzerland) · 2023Article
- Models of enzyme inhibition and apparent dissociation constants from kinetic analysis to study the differential inhibition of aldose reductase.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Extracts of Fruits and Plants Cultivated In Vitro ofPlants (Basel, Switzerland) · 2022Article
- Article
- In Search of Differential Inhibitors of Aldose Reductase.Biomolecules · 2022Review
- Nature-InspiredBiomolecules · 2022Article
- Perspective on the Structural Basis for Human Aldo-Keto Reductase 1B10 Inhibition.Metabolites · 2021Review
- Article
- In Search for Multi-Target Ligands as Potential Agents for Diabetes Mellitus and Its Complications-A Structure-Activity Relationship Study on Inhibitors of Aldose Reductase and Protein Tyrosine Phosphatase 1B.Molecules (Basel, Switzerland) · 2021Article
- Aldose Reductase: An Emerging Target for Development of Interventions for Diabetic Cardiovascular Complications.Frontiers in endocrinology · 2021Review
- Intra-site differential inhibition of multi-specific enzymes.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Aldose Reductase Differential Inhibitors in Green Tea.Biomolecules · 2020Article
- Soyasaponins from Zolfino bean as aldose reductase differential inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Stereoselectivity of Aldose Reductase in the Reduction of Glutathionyl-Hydroxynonanal Adduct.Antioxidants (Basel, Switzerland) · 2019Article
- Synthesis and Aldose Reductase Inhibitory Effect of Some New Hydrazinecarbothioamides and 4-Thiazolidinones Bearing an Imidazo[2,1-Turkish journal of pharmaceutical sciences · 2019Article
- The use of dimethylsulfoxide as a solvent in enzyme inhibition studies: the case of aldose reductase.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Thiol oxidase ability of copper ion is specifically retained upon chelation by aldose reductase.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
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Authors and funding
9 authors.
Funding
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Abstract
Aldose reductase (AR) is an NADPH-dependent reductase, which acts on a variety of hydrophilic as well as hydrophobic aldehydes. It is currently defined as the first enzyme in the so-called polyol pathway, in which glucose is transformed into sorbitol by AR and then to fructose by an NAD(+)-dependent dehydrogenase. An exaggerated flux of glucose through the polyol pathway (as can occur in diabetes) with the subsequent accumulation of sorbitol, was originally proposed as the basic event in the aethiology of secondary diabetic complications. For decades this has meant targeting the enzyme for a specific and strong inhibition. However, the ability of AR to reduce toxic alkenals and alkanals, which are products of oxidative stress, poses the question of whether AR might be better classified as a detoxifying enzyme, thus raising doubts as to the unequivocal advantages of inhibiting the enzyme. This paper provides evidence of the possibility for an effective intervention on AR activity through an intra-site differential inhibition. Examples of a new generation of aldose reductase "differential" inhibitors (ARDIs) are presented, which can preferentially inhibit the reduction of either hydrophilic or hydrophobic substrates. Some selected inhibitors are shown to preferentially inhibit enzyme activity on glucose or glyceraldehyde and 3-glutathionyl-4-hydroxy-nonanal, but are less effective in reducing 4-hydroxy-2-nonenal. We question the efficacy of D, L-glyceraldehyde, the substrate commonly used in in vitro inhibition AR studies, as an in vitro reference AR substrate when the aim of the investigation is to impair glucose reduction.
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