title: Aldose reductase inhibitor, epalrestat, reduces lipid hydroperoxides in type 2 diabetes.
abstract: The increased flux of polyol pathway induced by hyperglycemia is implicated in the pathogenesis of various complications associated with diabetic, which results in increased oxidative stress. Because oxidative stress causes tissue damage in patients with diabetes, searching for an effective strategy to reduce oxidative stress in clinical setting is important in order to prevent diabetic complications. The aim of this study was to evaluate the effects of aldose reductase inhibition on oxidative stress in patients with type 2 diabetes mellitus. The subjects of this study were 21 patients with type 2 diabetes. We compared the levels of various oxidative stress markers and antioxidants including plasma thiobarbituric acid-reactive substances, malondialdehyde-modified low-density lipoprotein, vitamin E, beta-carotene and lipid hydroperoxides in erythrocytes at baseline with those measured after a 3-month course of epalrestat (150 mg/day), an aldose reductase inhibitor. While administration of epalrestat did not result in significant changes in plasma thiobarbituric acid-reactive substances, malondialdehyde-modified low-density lipoprotein, vitamin E, or beta-carotene, it significantly reduced lipid hydroperoxides in erythrocytes. Given the importance of measuring lipid hydroperoxides in erythrocytes as an index of oxidative stress, these results highlight the potential usefulness of epalrestat in reducing oxidative stress in type 2 diabetes mellitus.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Ohmura
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.forename: Kosuke
authors.initials: K
authors.lastname: Azuma
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Akio
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Fuki
authors.initials: F
authors.lastname: Ikeda
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
mesh_terms: D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D053778:Thiazolidines / Q000494:pharmacology* / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014810:Vitamin E / Q000097:blood; D019207:beta Carotene / Q000097:blood
chemical_list: D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D053778:Thiazolidines; D017392:Thiobarbituric Acid Reactive Substances; D019207:beta Carotene; D014810:Vitamin E; C038131:epalrestat; D008315:Malondialdehyde; D012236:Rhodanine; D000449:Aldehyde Reductase