Edaravone Suppresses Reperfusion Injury following Leg Ischemia in Rats: A Transmission Electron Microscopic Study

Abstract

It is well known that free radicals cause reperfusion injury following leg ischemia. We showed that the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Osaka, Japan), might suppress reperfusion injury in rat. In this study, we used transmission electron microscope (TEM) to investigate how edaravone suppresses reperfusion injury by focusing on glycogen granules in the lower extremity muscles. Male Lewis rats (582 ± 35 g) were intraperitoneally injected with edaravone (3.0 mg/kg, edaravone group, n = 5) or the same dose of saline (control group, n = 5). The rat reperfusion injury models were induced by clamping the bilateral common femoral arteries for 5 hours and then declamping. The muscles were harvested at 5 hours after the start of reperfusion. Under a TEM (JEM-1220, Nippon Denshi Co., Tokyo, Japan), we counted the number of glycogen granules at ×50,000 magnification on each five different fields. The TEM sections from the control group showed a marked loss of glycogen granules and swollen mitochondria. In contrast, the TEM sections from the edaravone group showed numerous glycogen granules and normal mitochondria. The mean density of glycogen granules in the edaravone group was significantly higher than that in the control group (88.5 ± 5.3 vs. 16.4 ± 3.1 particles/µm², p < 0.001). Our TEM results confirmed that edaravone suppresses reperfusion injury following leg ischemia by maintaining the glycogen granules in muscles.

Keywords

reperfusion injury - free radical - edaravone

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