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J Ocul Pharmacol Ther. 2017 Jan/Feb;33(1):34-41. doi: 10.1089/jop.2016.0103. Epub 2016 Nov 11.

Epalrestat, an Aldose Reductase Inhibitor Prevents Glucose-Induced Toxicity in Human Retinal Pigment Epithelial Cells In Vitro.

Author information

  • 11 Department of Ocular Pharmacology, Dr. G. Venkataswamy Eye Research Institute , Madurai, India .
  • 22 Department of Immunology & Stem Cell Biology, Dr. G. Venkataswamy Eye Research Institute , Madurai, India .
  • 33 Molecular Genetics, Aravind Medical Research Foundation (AMRF), Dr. G. Venkataswamy Eye Research Institute , Madurai, India .

Abstract

PURPOSE:

Aldose reductase (ALR), the first and rate-limiting enzyme involved in polyol pathway plays a central role in diabetes and its related complications, including diabetic retinopathy (DR). Inhibition of ALR may also be an ideal target for reducing the deleterious effects of DR. Therefore, the purpose of the present study was to investigate the protective effect of epalrestat (EPL), ALR inhibitor on glucose-induced toxicity in ARPE-19 cells.

METHODS:

ARPE-19 cells were challenged with normal glucose (NG, 5 mM) and high glucose (HG1, 25 mM and HG2, 50 mM) in the presence or absence of EPL. ALR and VEGF165 expression in retinal pigment epithelial (RPE) cells under experimental conditions were quantified by real-time polymerase chain reaction using SYBR Green chemistry. Vascular endothelial growth factor (VEGF) secretion in the cell supernatant was measured by Sandwich ELISA. Cytotoxicity of EPL was assessed by MTT assay. ALR inhibitory activity, apoptosis, and sorbitol accumulation were also investigated.

RESULTS:

EPL at studied concentration did not show any toxicity to RPE cells and showed as maximum as 65% ALR inhibition under high glucose condition (HG1). The presence of EPL significantly reduced ALR expression and VEGF levels as induced by high glucose in ARPE-19 cells.

CONCLUSION:

Inhibition of ALR appeared to be beneficial in reducing diabetes-related complications in RPE cells under high glucose condition.

KEYWORDS:

ARPE-19; VEGF; aldose reductase; epalrestat; high glucose toxicity

PMID:
27835059
DOI:
10.1089/jop.2016.0103
[PubMed - in process]
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