Protective Effect of Edaravone Against Oxidative Stress in C2C12 Myoblast and Impairment of Skeletal Muscle Regeneration Exposed to Ischemic Injury in Ob/ob Mice

依达拉奉对 Ob/ob 小鼠 C2C12 成肌细胞氧化应激及缺血性损伤骨骼肌再生障碍的保护作用

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作者:Takuya Nakanishi, Masaya Tsujii, Takahiro Asano, Takahiro Iino, Akihiro Sudo

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.

Conclusion

Edaravone attenuated the oxidative stress on C2C12 myoblasts, and was effective to regeneration of skeletal muscles after ischemia in ob/ob mice.

Methods

In C2C12 myoblasts, oxidative stress was induced by the exposure to 250 μM H2O2 for 4 h with or without pretreatment of 100 μM 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.

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