Protective effect of epalrestat against high glucose-induced endothelial cell injuries.
- Author:
Fang WANG
1
;
Quan HONG
;
Guiyang LIU
Author Information
- Publication Type:Journal Article
- MeSH: Aldehyde Reductase; antagonists & inhibitors; Cells, Cultured; Endothelium, Vascular; drug effects; metabolism; Enzyme Inhibitors; pharmacology; Glucose; adverse effects; Human Umbilical Vein Endothelial Cells; cytology; drug effects; Humans; NADPH Oxidase 4; NADPH Oxidases; metabolism; Nitric Oxide Synthase Type III; metabolism; RNA, Messenger; genetics; Rhodanine; analogs & derivatives; pharmacology; Thiazolidines; pharmacology
- From: Journal of Southern Medical University 2012;32(7):940-943
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the protective effect of epalrestat against endothelial cell injuries induced by high glucose.
METHODSHuman 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).
RESULTSCompared 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.
CONCLUSIONSHigh 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.
