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Background: The aims of this study were to analyze the effects of the administration of edaravone on C2C12 myoblasts exposed to oxidative stress; to evaluate the skeletal muscles in ob/ob mice; and to analyze the effect of the administration of edaravone in the regeneration of skeletal muscle after ischemic injury.Methods: In C2C12 myoblasts, oxidative stress was induced by the exposure to 250μM H2O2 for 4h with or without pretreatment of 100μM edaravone. Thereafter, the viability and expression of TNF-α were analyzed by MTS assay and PCR, respectively. Furthermore, an in vivo study was performed on male C57/BL6-ob/ob mice (10 weeks old) and the respective control mice. The skeletal muscles of tibialis anterior and gastrocnemius were excised for histological analysis and TBARS assay after the measurement of blood flow. In addition, the regeneration of the skeletal muscles was analyzed for the expression of MyoD 7 days after the ligation of the right femoral artery.Results: Edaravone significantly inhibited the reduction of the viability as well as upregulation of TNF-α expression by treatment with H2O2. In ob/ob mice, wet weight of muscles was significantly lower than that in control mice. In histology, ob/ob mice had significantly less multi-angle shaped myofibers and a significantly high level of MDA. Furthermore, MyoD expression was lower in ob/ob mice than in control mice after the ischemic injury, while edaravone (3 mg/kg) increasingly enhanced MyoD expression.Conclusion: Edaravone attenuated the oxidative stress on C2C12 myoblasts, and was effective to regeneration of skeletal muscles after ischemia in ob/ob mice.
本文/Department of Orthopaedic Surgery, Graduate School of Medicine, Mie University, Tsu, Japan
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DOIinfo:doi/10.3389/fphys.2019.01596
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