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 in 26 subjects with either type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg orally twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 weeks duration, with a 4 week washout between. 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 when compared to 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 affect endothelium-dependent vasodilation in patients with diabetes mellitus.
- Endothelial Function
- Oxidative Stress
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology