TY - JOUR
T1 - Ebselen does not improve oxidative stress and vascular function in patients with diabetes
T2 - A randomized, crossover trial
AU - Beckman, Joshua A.
AU - Goldfine, Allison B.
AU - Leopold, Jane A.
AU - Creager, Mark A.
N1 - Funding Information:
This study was supported by National Institutes of Health Grants K23 HL-04169 and P30 DK-036836.
Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Endothelial function
KW - Oxidative stress
KW - Type 1 diabetes mellitus
KW - Type 2 diabetes mellitus
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U2 - 10.1152/ajpheart.00504.2016
DO - 10.1152/ajpheart.00504.2016
M3 - Article
C2 - 27765750
AN - SCOPUS:85005987270
SN - 0363-6135
VL - 311
SP - H1431-H1436
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6
ER -