Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress

• Published in: PloS one Vol. 8; no. 9; p. e76025
• Main Authors: Li, Wenlu, Xu, Hongjiao, Hu, Yangmin, He, Ping, Ni, Zhenzhen, Xu, Huimin, Zhang, Zhongmiao, Dai, Haibin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.09.2013; Public Library of Science (PLoS)
• Subjects: Advanced glycosylation end products; Age; Antipyrine - analogs & derivatives; Antipyrine - pharmacology; Apoptosis; Blotting, Western; Brain; Brain - blood supply; Brain - cytology; Brain injury; Cell injury; Clinical trials; Deoxyribonucleic acid; Deprivation; Diabetes; Diabetes Complications - metabolism; Diabetes mellitus; DNA; Endothelial cells; Endothelial Cells - metabolism; Free radicals; Glucose; Glycation End Products, Advanced - metabolism; Glycosylation; Health risks; Hospitals; Humans; Hyperglycemia; Injuries; Ischemia; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Medical research; Medicine; Microvasculature; Microvessels - cytology; Oxidative stress; Oxidative Stress - physiology; Oxygen; Pharmacy; Polyclonal antibodies; Proteins; Pyruvaldehyde; Pyruvaldehyde - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptor for Advanced Glycation End Products; Receptors, Immunologic - metabolism; Rhodamine; Rhodamine 123; Rodents; Stroke; Tetrazolium Salts; Thiazoles; Western blotting; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076025

Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.