title: Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.
abstract: Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.
authors.affiliation: Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tennessee; Joshua.a.beckman@vanderbilt.edu.
authors.forename: Joshua A
authors.identifier: 0000-0001-8332-8439
authors.initials: JA
authors.lastname: Beckman
authors.affiliation: Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; and.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Leopold
authors.affiliation: Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D016022:Case-Control Studies; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D054833:Isoindoles; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology; D010991:Plethysmography; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D010277:Parasympathomimetics; D016210:Methacholine Chloride; C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; C042986:ebselen; D014443:Tyrosine; D015237:Dinoprost; D005978:Glutathione
keywords: endothelial function; oxidative stress; type 1 diabetes mellitus; type 2 diabetes mellitus