Muscles Susceptibility to Ischemia-Reperfusion Injuries Depends on Fiber Type Specific Antioxidant Level

Charles, Anne-Laure and Guilbert, Anne-Sophie and Guillot, Max and Talha, Samy and Lejay, Anne and Meyer, Alain and Kindo, Michel and Wolff, Valérie and Bouitbir, Jamal and Zoll, Joffrey and Geny, Bernard. (2017) Muscles Susceptibility to Ischemia-Reperfusion Injuries Depends on Fiber Type Specific Antioxidant Level. Frontiers in physiology, 8. p. 52.

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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,; n; = 11) on both; gastrocnemius; and; soleus; muscles, as compared to control animals (C,; n; = 11). Further, we investigated whether tempol, an antioxidant mimicking superoxide dismutase, might compensate a reduced defense system, likely characterizing glycolytic muscles (IR-Tempol,; n; = 7). In the glycolytic; gastrocnemius; muscle, as compared to control, ischemia-reperfusion significantly decreased mitochondrial respiration (-30.28 ± 6.16%,; p; = 0.003), increased reactive oxygen species production (+79.15 ± 28.72%,; p; = 0.04), and decreased reduced glutathione (-28.19 ± 6.80%,; p; = 0.011). Less deleterious effects were observed in the oxidative; soleus; 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; gastrocnemius vs; . 1.24 ± 0.08 μmol L; -1; g; -1; in; soleus; ). 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften
UniBasel Contributors:Bouitbir, Jamal
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Frontiers Media
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Aug 2020 12:53
Deposited On:26 Aug 2020 12:53

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