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Renoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury.
El Gamal, Heba; Eid, Ali Hussein; Munusamy, Shankar.
Afiliação
  • El Gamal H; College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
  • Eid AH; Department of Pharmacology and Toxicology, School of Medicine, American University of Beirut, Beirut, Lebanon.
  • Munusamy S; College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
Biomed Res Int ; 2017: 5903105, 2017.
Article em En | MEDLINE | ID: mdl-28386557
ABSTRACT
Diabetic nephropathy (DN) is the leading cause of end stage renal disease worldwide. Increased glucose flux into the aldose reductase (AR) pathway during diabetes was reported to exert deleterious effects on the kidney. The objective of this study was to investigate the renoprotective effects of AR inhibition in high glucose milieu in vitro. Rat renal tubular (NRK-52E) cells were exposed to high glucose (30 mM) or normal glucose (5 mM) media for 24 to 48 hours with or without the AR inhibitor epalrestat (1 µM) and assessed for changes in Akt and ERK1/2 signaling, AR expression (using western blotting), and alterations in mitochondrial membrane potential (using JC-1 staining), cell viability (using MTT assay), and cell cycle. Exposure of NRK-52E cells to high glucose media caused acute activation of Akt and ERK pathways and depolarization of mitochondrial membrane at 24 hours. Prolonged high glucose exposure (for 48 hours) induced AR expression and G1 cell cycle arrest and decreased cell viability (84% compared to control) in NRK-52E cells. Coincubation of cells with epalrestat prevented the signaling changes and renal cell injury induced by high glucose. Thus, AR inhibition represents a potential therapeutic strategy to prevent DN.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rodanina / Aldeído Redutase / Diabetes Mellitus Experimental / Nefropatias Diabéticas / Tiazolidinas Limite: Animals / Humans Idioma: En Revista: Biomed Res Int Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rodanina / Aldeído Redutase / Diabetes Mellitus Experimental / Nefropatias Diabéticas / Tiazolidinas Limite: Animals / Humans Idioma: En Revista: Biomed Res Int Ano de publicação: 2017 Tipo de documento: Article