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Open Access Research article

Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb

Kazuichiro Hori1, Masaya Tsujii1*, Takahiro Iino1, Haruhiko Satonaka1, Takeshi Uemura1, Koji Akeda1, Masahiro Hasegawa1, Atsumasa Uchida2 and Akihiro Sudo1

Author Affiliations

1 Department of Orthopaedic Surgery, Graduate School of Medicine Mie University, 2-174 Edobashi, Tsu city, Mie prefecture 514-8507, Japan

2 Mie University, Mie, Japan

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BMC Musculoskeletal Disorders 2013, 14:113  doi:10.1186/1471-2474-14-113

Published: 27 March 2013

Abstract

Background

Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The purposes of this study were 1) to assess the histological findings of gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model mice, 2) to histologically analyze whether a single pretreatment of edaravone inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the effect of oxidative stress on these muscles.

Methods

C57BL6 mice were divided in two groups, with one group receiving 3 mg/kg intraperitoneal injections of edaravone (I/R + Ed group) and the other group receiving an identical amount of saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway, in addition to having potent antioxidant effects against ischemia reperfusion. The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72 hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were removed for histological evaluation and biochemical analysis.

Results

This model of I/R injury was highly reproducible in histologic muscle damage. In the histologic damage score, the mean muscle fibers and inflammatory cell infiltration in the I/R + Ed group were significantly less than the corresponding values of observed in the I/R group. Thus, pretreatment with edaravone was observed to have a protective effect on muscle damage after a period of I/R in mice. In addition, the mean muscle injury score in the I/R + Ed group was also significantly less than the I/R group. In the I/R + Ed group, the mean malondialdehyde (MDA) level was lower than in the I/R group and western-blotting revealed that edaravone pretreatment decreased the level of inducible nitric oxide synthase (iNOS) expression.

Conclusions

Edaravone was found to have a protective effect against I/R injury by directly inhibiting lipid peroxidation of the myocyte by free radicals in skeletal muscles and may also reduce the secondary edema and inflammatory infiltration incidence of oxidative stress on tissue.

Keywords:
Ischemia-reperfusion injury; Skeletal muscle; Free radical scavenger; Edaravone; iNOS