title: [Protective effect of epalrestat against high glucose-induced endothelial cell injuries].
abstract: OBJECTIVE
  To study the protective effect of epalrestat against endothelial cell injuries induced by high glucose.
  
  
  METHODS
  Human umbilical vein endothelial cells were pretreated with epalrestat (0.1 µmol/L) for 30 min followed by exposure to high glucose for 8 h. NO concentration in the cell culture supernatant was assayed using chemiluminescence method following the exposure. Real-time PCR and Western blotting were used to detect eNOS mRNA and protein expression levels and the protein expressions of AR gene (the target gene of epalrestat) and NOX4 (the upstream gene of NO).
  
  
  RESULTS
  Compared with mannitol treatment, an 8-h exposure to high glucose caused significantly decreased NO levels and eNOS mRNA and protein expression in the vascular endothelial cells (P<0.05). Pretreatment with epalrestat prior to high glucose exposure resulted in elevated eNOS mRNA and protein expression levels and NO up-regulation in the cell culture as compared with the glucose exposure alone group  (P<0.05), causing also decreased expression of AR and NOX4 in the cells.
  
  
  CONCLUSIONS
  High glucose can induce endothelial cell damage characterized by a lowered level of NO secretion. Epalrestat can protect the endothelial cells against high glucose-induced injury by inhibiting the expression of AR and NOX4.
authors: Department of Pharmacy, First Affiliated Hospital of General Hospital of PLA, Beijing 100048, China. wangfang304@163.com
authors: Fang
authors: F
authors: Wang
authors: Quan
authors: Q
authors: Hong
authors: Guiyang
authors: G
authors: Liu
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000009:adverse effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D000449:Aldehyde Reductase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D005947:Glucose