EPR spectroscopic evidence of iron-catalysed free radical formation in chronic mountain sickness: Dietary causes and vascular consequences.

Autor: Bailey DM; Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Wales, UK. Electronic address: damian.bailey@southwales.ac.uk., Culcasi M; Aix Marseille Univ, CNRS, ICR, UMR, 7273, Marseille, France., Filipponi T; Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Wales, UK., Brugniaux JV; Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Wales, UK; HP2 Laboratory, INSERM U1300, Grenoble Alpes University, Grenoble, France., Stacey BS; Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Wales, UK., Marley CJ; Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Wales, UK., Soria R; Department of Cardiology and Biomedical Research, University Hospital, Bern, Switzerland., Rimoldi SF; Department of Cardiology and Biomedical Research, University Hospital, Bern, Switzerland., Cerny D; Department of Cardiology and Biomedical Research, University Hospital, Bern, Switzerland., Rexhaj E; Department of Cardiology and Biomedical Research, University Hospital, Bern, Switzerland., Pratali L; Institute of Clinical Physiology, Pisa, Italy., Salmòn CS; Instituto Bolivano de Biologia de Altura, La Paz, Bolivia., Jáuregui CM; Instituto Bolivano de Biologia de Altura, La Paz, Bolivia., Villena M; Instituto Bolivano de Biologia de Altura, La Paz, Bolivia., Villafuerte F; Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru., Rockenbauer A; Institute of Materials and Environmental Chemistry, Research Center for Natural Sciences, 1117, Budapest, Hungary., Pietri S; Aix Marseille Univ, CNRS, ICR, UMR, 7273, Marseille, France., Scherrer U; Department of Cardiology and Biomedical Research, University Hospital, Bern, Switzerland; Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile., Sartori C; Department of Internal Medicine, University Hospital, UNIL-Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2022 May 01; Vol. 184, pp. 99-113. Date of Electronic Publication: 2022 Apr 06.
DOI: 10.1016/j.freeradbiomed.2022.03.028
Abstrakt: Chronic mountain sickness (CMS) is a high-altitude (HA) maladaptation syndrome characterised by elevated systemic oxidative-nitrosative stress (OXNOS) due to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability. To better define underlying mechanisms and vascular consequences, this study compared healthy male lowlanders (80 m, n = 10) against age/sex-matched highlanders born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 10) and without (CMS-, n = 10) CMS. Cephalic venous blood was assayed using electron paramagnetic resonance spectroscopy and reductive ozone-based chemiluminescence. Nutritional intake was assessed via dietary recall. Systemic vascular function and structure were assessed via flow-mediated dilatation, aortic pulse wave velocity and carotid intima-media thickness using duplex ultrasound and applanation tonometry. Basal systemic OXNOS was permanently elevated in highlanders (P = <0.001 vs. lowlanders) and further exaggerated in CMS+, reflected by increased hydroxyl radical spin adduct formation (P = <0.001 vs. CMS-) subsequent to liberation of free 'catalytic' iron consistent with a Fenton and/or nucleophilic addition mechanism(s). This was accompanied by elevated global protein carbonylation (P = 0.046 vs. CMS-) and corresponding reduction in plasma nitrite (P = <0.001 vs. lowlanders). Dietary intake of vitamins C and E, carotene, magnesium and retinol were lower in highlanders and especially deficient in CMS + due to reduced consumption of fruit and vegetables (P = <0.001 to 0.028 vs. lowlanders/CMS-). Systemic vascular function and structure were also impaired in highlanders (P = <0.001 to 0.040 vs. lowlanders) with more marked dysfunction observed in CMS+ (P = 0.035 to 0.043 vs. CMS-) in direct proportion to systemic OXNOS (r = -0.692 to 0.595, P = <0.001 to 0.045). Collectively, these findings suggest that lifelong exposure to iron-catalysed systemic OXNOS, compounded by a dietary deficiency of antioxidant micronutrients, likely contributes to the systemic vascular complications and increased morbidity/mortality in CMS+. TRIAL REGISTRY: ClinicalTrials.gov; No: NCT01182792; URL: www.clinicaltrials.gov.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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