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AuthorEl Gamal, Heba
AuthorEid, Ali Hussein
AuthorMunusamy, Shankar
Available date2017-04-30T05:33:37Z
Publication Date2017-03
Publication NameBioMed Research Internationalen_US
Identifierhttp://dx.doi.org/10.1155/2017/5903105
CitationHeba El Gamal, Ali Hussein Eid, and Shankar Munusamy, “Renoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury,” BioMed Research International, vol. 2017, Article ID 5903105, 11 pages, 2017
ISSN2314-6133
URIhttp://hdl.handle.net/10576/5474
AbstractDiabetic 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 muM) 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.
SponsorThis manuscript is based on the thesis of Heba El Gamal, and this study was funded by Intramural Student Research Grants awarded by the Office of Academic Research, Qatar University (nos. QUST-CPH-SPR-12/13-4, QUST-CPH-FALL-13/14- 5, QUST-CPH-SPR-13/14-7, QUST-CPH-FALL-14/15-6, and QUST-CPH-SPR-14/15-15).
Languageen
PublisherHindawi
SubjectKidney
SubjectDiabetic nephropathy
SubjectAldose reductase
SubjectEpalrestat
SubjectMitochondrial membrane potential
SubjectHigh glucose.
TitleRenoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury
TypeArticle
Volume Number2017
ESSN2314-6141


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