AUTHOR=CHARLES Anne-Laure , Guilbert Anne-Sophie , Guillot Max , Talha Samy , Lejay Anne , Meyer Alain , Kindo Michel , wolff valerie , Bouitbir Jamal , Zoll Joffrey , GENY Bernard 

TITLE=Muscles susceptibility to ischemia-reperfusion injuries depends on fiber type specific antioxidant level

JOURNAL=Frontiers in Physiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00052

DOI=10.3389/fphys.2017.00052

ISSN=1664-042X

ABSTRACT=<p>Muscle injury resulting from ischemia-reperfusion largely aggravates patient prognosis but whether and how muscle phenotype modulates ischemia-reperfusion-induced mitochondrial dysfunction remains to be investigated. We challenged the hypothesis that glycolytic muscles are more prone to ischemia-reperfusion-induced injury than oxidative skeletal muscles. We therefore determined simultaneously the effect of 3 h of ischemia induced by aortic clamping followed by 2 h of reperfusion (IR, <italic>n</italic> = 11) on both <italic>gastrocnemius</italic> and <italic>soleus</italic> muscles, as compared to control animals (C, <italic>n</italic> = 11). Further, we investigated whether tempol, an antioxidant mimicking superoxide dismutase, might compensate a reduced defense system, likely characterizing glycolytic muscles (IR-Tempol, <italic>n</italic> = 7). In the glycolytic <italic>gastrocnemius</italic> muscle, as compared to control, ischemia-reperfusion significantly decreased mitochondrial respiration (−30.28 ± 6.16%, <italic>p</italic> = 0.003), increased reactive oxygen species production (+79.15 ± 28.72%, <italic>p</italic> = 0.04), and decreased reduced glutathione (−28.19 ± 6.80%, <italic>p</italic> = 0.011). Less deleterious effects were observed in the oxidative <italic>soleus</italic> muscle (−6.44 ± 6.30%, +4.32 ± 16.84%, and −8.07 ± 10.84%, respectively), characterized by enhanced antioxidant defenses (0.63 ± 0.05 in <italic>gastrocnemius vs</italic>. 1.24 ± 0.08 μmol L<sup>−1</sup> g<sup>−1</sup> in <italic>soleus</italic>). Further, when previously treated with tempol, glycolytic muscle was largely protected against the deleterious effects of ischemia-reperfusion. Thus, oxidative skeletal muscles are more protected than glycolytic ones against ischemia-reperfusion, thanks to their antioxidant pool. Such pivotal data support that susceptibility to ischemia-reperfusion-induced injury differs between organs, depending on their metabolic phenotypes. This suggests a need to adapt therapeutic strategies to the specific antioxidant power of the target organ to be protected.</p>