Next Article in Journal
The Role of the Plant Antioxidant System in Drought Tolerance
Next Article in Special Issue
Aging Exacerbates Ischemia-Reperfusion-Induced Mitochondrial Respiration Impairment in Skeletal Muscle
Previous Article in Journal
Polyphenolic Composition of Rosa canina, Rosa sempervivens and Pyrocantha coccinea Extracts and Assessment of Their Antioxidant Activity in Human Endothelial Cells
Previous Article in Special Issue
Protective Effect of the Hexanic Extract of Eryngium carlinae Inflorescences In Vitro, in Yeast, and in Streptozotocin-Induced Diabetic Male Rats
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

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

1
Unistra, Fédération de Médecine Translationnelle, Equipe d’Accueil 3072, « Mitochondrie, Stress oxydant et Protection Musculaire », Institut de Physiologie, 67000 CEDEX, France
2
Hôpitaux Universitaires de Strasbourg, Service de Physiologie et d’Explorations Fonctionnelles, 67000 Strasbourg, France
3
Hôpitaux Universitaires de Strasbourg, Service de Chirurgie vasculaire et de transplantation rénale, 67000 Strasbourg, France
4
IRMA, équipe MoCo et LabEx IRMIA, 7 rue René Descartes, 67084 Strasbourg CEDEX, France
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(4), 93; https://doi.org/10.3390/antiox8040093
Received: 28 March 2019 / Revised: 4 April 2019 / Accepted: 5 April 2019 / Published: 7 April 2019
(This article belongs to the Special Issue Antioxidants in Oxidative Stress Diseases)
  |  
PDF [1594 KB, uploaded 7 April 2019]
  |  

Abstract

Lower-limb ischemia-reperfusion (IR) is frequent and associated with significant morbidity and mortality. Phosphodiesterase 5 inhibitors demonstrated antioxidant and beneficial effects in several organs submitted to IR, but their effects on muscle mitochondrial functions after lower-limb IR are unknown. Unilateral hindlimb IR (2 h tourniquet followed by 2 h reperfusion) without or with sildenafil (1mg/kg ip 30 minutes before ischemia) was performed in 18 mice. Maximal oxidative capacity (VMax), relative contribution of the mitochondrial respiratory chain complexes, calcium retention capacity (CRC)—a marker of apoptosis—and reactive oxygen species (ROS) production were determined using high-resolution respirometry, spectrofluorometry, and electron paramagnetic resonance in gastrocnemius muscles from both hindlimbs. IR significantly reduced mitochondrial VMax (from 11.79 ± 1.74 to 4.65 ± 1.11 pmol/s*mg wet weight (ww), p < 0.05, −50.2 ± 16.3%) and CRC (from 2.33 ± 0.41 to 0.84 ± 0.18 µmol/mg dry weight (dw), p < 0.05; −61.1 ± 6.8%). ROS tended to increase in the ischemic limb (+64.3 ± 31.9%, p = 0.08). Although tending to reduce IR-related ROS production (−42.4%), sildenafil failed to reduce muscle mitochondrial dysfunctions (−63.3 ± 9.2%, p < 0.001 and −55.2 ± 7.6% p < 0.01 for VMax, and CRC, respectively). In conclusion, lower limb IR impaired skeletal muscle mitochondrial function, but, despite tending to reduce ROS production, pharmacological preconditioning with sildenafil did not show protective effects. View Full-Text
Keywords: cyclic nucleotide phosphodiesterase; sildenafil; muscle; ischemia; reperfusion; peripheral arterial disease; mitochondria; reactive oxygen species; oxidative stress; calcic retention capacity cyclic nucleotide phosphodiesterase; sildenafil; muscle; ischemia; reperfusion; peripheral arterial disease; mitochondria; reactive oxygen species; oxidative stress; calcic retention capacity
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Tetsi, L.; Charles, A.-L.; Georg, I.; Goupilleau, F.; Lejay, A.; Talha, S.; Maumy-Bertrand, M.; Lugnier, C.; Geny, B. Effect of the Phosphodiesterase 5 Inhibitor Sildenafil on Ischemia-Reperfusion-Induced Muscle Mitochondrial Dysfunction and Oxidative Stress. Antioxidants 2019, 8, 93.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Antioxidants EISSN 2076-3921 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top