Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial

Author:

Beckman Joshua A.1ORCID,Goldfine Allison B.2,Leopold Jane A.3,Creager Mark A.4

Affiliation:

1. Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tennessee;

2. Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts;

3. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; and

4. Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

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.

Funder

NHLBI

NIH

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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