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Effect of the Phosphodiesterase 5 Inhibitor Sildenafil on Ischemia-Reperfusion-Induced Muscle Mitochondrial Dysfunction and Oxidative Stress
Open AccessArticle

Aging Exacerbates Ischemia-Reperfusion-Induced Mitochondrial Respiration Impairment in Skeletal Muscle

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Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Institut de Physiologie, Equipe d’Accueil EA3072 “Mitochondrie, Stress Oxydant et Protection Musculaire”, Université de Strasbourg, 67000 Strasbourg, France
2
Service de Physiologie et d’Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Nouvel Hôpital Civil, CHRU de Strasbourg, 67000 Strasbourg, France
3
Service de Chirurgie Cardiaque, Pôle de Pathologie Cardiaque, Nouvel Hôpital Civil, CHRU de Strasbourg, 67000 Strasbourg, France
4
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch, France
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(6), 168; https://doi.org/10.3390/antiox8060168
Received: 17 May 2019 / Revised: 31 May 2019 / Accepted: 5 June 2019 / Published: 8 June 2019
(This article belongs to the Special Issue Antioxidants in Oxidative Stress Diseases)
Cycles of ischemia-reperfusion (IR) that occur during peripheral arterial disease (PAD) are associated with significant morbi-mortality, and aging is an irreversible risk factor of PAD. However, the effects of advanced age on IR-induced skeletal muscle mitochondrial dysfunction are not well known. Young and aged mice were therefore submitted to hindlimb IR (2 h ischemia followed by 2 h reperfusion). Skeletal muscle mitochondrial respiration, calcium retention capacity (CRC) and reactive oxygen species (ROS) production were determined using high resolution respirometry, spectrofluorometry and electronic paramagnetic resonance. IR-induced impairment in mitochondrial respiration was enhanced in old animals (VADP; from 33.0 ± 2.4 to 18.4 ± 3.8 and 32.8 ± 1.3 to 5.9 ± 2.7 pmol/s/mg wet weight; −44.2 ± 11.4% vs. −82.0 ± 8.1%, in young and aged mice, respectively). Baseline CRC was lower in old animals and IR similarly decreased the CRC in both groups (from 11.8 ± 0.9 to 4.6 ± 0.9 and 5.5 ± 0.9 to 2.1 ± 0.3 µmol/mg dry weight; −60.9 ± 7.3 and −60.9 ± 4.6%, in young and aged mice, respectively). Further, IR-induced ROS production tended to be higher in aged mice. In conclusion, aging exacerbated the deleterious effects of IR on skeletal muscle mitochondrial respiration, potentially in relation to an increased oxidative stress. View Full-Text
Keywords: peripheral arterial disease; ischemia-reperfusion; skeletal muscle; mitochondria; respiration; calcium; oxidative stress; reactive oxygen species; aging peripheral arterial disease; ischemia-reperfusion; skeletal muscle; mitochondria; respiration; calcium; oxidative stress; reactive oxygen species; aging
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Paradis, S.; Charles, A.-L.; Georg, I.; Goupilleau, F.; Meyer, A.; Kindo, M.; Laverny, G.; Metzger, D.; Geny, B. Aging Exacerbates Ischemia-Reperfusion-Induced Mitochondrial Respiration Impairment in Skeletal Muscle. Antioxidants 2019, 8, 168.

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