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. 2016 Dec;10:200-205.
doi: 10.1016/j.redox.2016.10.017. Epub 2016 Oct 27.

The Mitochondria-Targeted Antioxidant MitoQ Modulates Oxidative Stress, Inflammation and Leukocyte-Endothelium Interactions in Leukocytes Isolated From Type 2 Diabetic Patients

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Free PMC article

The Mitochondria-Targeted Antioxidant MitoQ Modulates Oxidative Stress, Inflammation and Leukocyte-Endothelium Interactions in Leukocytes Isolated From Type 2 Diabetic Patients

Irene Escribano-Lopez et al. Redox Biol. .
Free PMC article

Abstract

It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA-IR, HbA1c, triglycerides, hs-CRP and lower HDL-c with respect to controls. Mitochondrial ROS production was enhanced in T2D patients and decreased by MitoQ. The antioxidant also increased GPX-1 levels and PMN rolling velocity and decreased PMN rolling flux and PMN adhesion in T2D patients. NFκB-p65 and TNFα were augmented in T2D and were both reduced by MitoQ treatment. Our findings support that the antioxidant MitoQ has an anti-inflammatory and antioxidant action in the leukocytes of T2D patients by decreasing ROS production, leukocyte-endothelium interactions and TNFα through the action of NFκB. These data suggest that mitochondria-targeted antioxidants such as MitoQ should be investigated as a novel means of preventing cardiovascular events in T2D patients.

Keywords: Endothelium; Inflammation; Leukocytes; MitoQ; Oxidative stress; Type 2 diabetes.

Figures

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Fig. 1
Fig. 1
(A) Levels of MitoSox oxidation in controls and T2D patients in presence and absence of MitoQ or decyl-TPP (30 min, 0.5 µM) and representative fluorescence microscopy images (B) Levels of GPX-1 (25 kDa) measured by Western blot in controls and T2D patients in presence and absence of MitoQ or decyl-TPP (30 min, 0.5 µM). * p<0.05 and **p<0.01vs control; ap<0.05 vs T2D patients.
Fig. 2
Fig. 2
Leukocyte/endothelium interactions in T2D patients and control subjects in presence and absence of MitoQ or decyl-TPP (30 min, 0.5 µM). (A) PMN rolling velocity (μmsecond-1), (B) rolling flux (PMN per minute) and (C) PMN adhesion (PMN per square millimetre). **p<0.01 and ***p<0.001 vs control. ap<0.05 and bp<0.01 vs T2D patients.
Fig. 3
Fig. 3
Evaluation of protein expression by Western blot of p65-NFκB (55 kDa) (A) and TNFα (23 kDa) (B) in T2D patients and control subjects in presence and absence of MitoQ or decyl-TPP (30 min, 0.5 µM). *p<0.05 vs control. ap<0.05 vs T2D patients.

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