The effect of antioxidants on glycated albumin-induced cytotoxicity in bovine retinal pericytes.
Loss of retinal pericytes is the initial deficit in the early stage of diabetic retinopathy. Glycated albumin (GA) forms under hyperglycemic conditions and exists in the retinal blood vessels of diabetic patients with retinopathy. In this study, using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction test, we investigated whether GA induces cytotoxicity in cultured bovine retinal pericytes, and whether the antioxidants, l-ascorbic acid, Trolox, and probucol, provide any protection from GA-mediated cytotoxicity. GA induced pericyte death in a dose-dependent manner. With increasing time, GA-induced cytotoxicity also increased despite no strict time dependence. Furthermore, this cell death was found to be mediated both by apoptosis, which was confirmed by apoptosis-specific fluorescent staining of nuclei and cell membranes, and mitochondrial damage, as elucidated by electron microscopy. All three antioxidants used in this study partially protected against GA-induced pericyte death, suggesting that oxidative stress plays a role in GA-induced pericyte death. The results indicate that GA induces cell death in cultured bovine retinal pericytes, and that certain antioxidants may reduce this cytotoxicity.
Kim
Jaetaek
J
Division of Endocrinology and Metabolism, Chung-Ang University Hospital, Seoul, Korea.
Kim
Kwang-seok
KS
Shinn
Jong-wook
JW
Oh
Yeon-sahng
YS
Kim
Heung-tae
HT
Jo
Inho
I
Shinn
Soon-hyun
SH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017127:Glycation End Products, Advanced; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D020286:Pericytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology; D012160:Retina; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012709:Serum Albumin / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D000093423:Glycated Serum Albumin
D000975:Antioxidants; D002839:Chromans; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D011341:Probucol; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000093423:Glycated Serum Albumin