Edaravone reduces mitochondrial damage due to reperfusion injury following leg ischemia in rats

Abstract

PURPOSE: Free radicals have been implicated in reperfusion injury. It was shown that the free radical scavenger edaravone might suppress reperfusion injury in rat extremities. The present study aimed to elucidate how edaravone suppresses reperfusion injury, focusing on its effect on the mitochondrial structure and glycogen storage in the lower extremity muscles.

METHODS: Sixteen male Lewis rats (mean [± SD] weight 497±32 g) were divided into two groups and injected with either 3.0 mg/kg of edaravone (edaravone group, n=8 rats) or the same dose of saline (control group, n=8 rats) into the peritoneal cavity. The rat reperfusion injury models were created by clamping the bilateral common femoral arteries for 5 h, then declamping. The muscles were harvested more than 5 h after the start of reperfusion. The mitochondrial damage, defined as mitochondrial swelling, was examined using a transmission electron microscope at ×30,000 original magnification (n=3 for each rat). Glycogen storage, defined as a positive periodic acid-Schiff stain area, was examined using computerized densitometry (n=5 sections for each rat).

RESULTS: The mitochondria in the control group demonstrated marked swelling (mean mitochondrial size = 0.169±0.059 μm²). However, the mitochondria in the edaravone group had significantly less swelling (mean mitochondrial size = 0.102±0.036 μm²; P<0.01). The mean percentage of positive periodic acid-Schiff stain was also significantly higher in the edaravone group than in the control group (51.7±6.8% versus 7.3±2.1%; P<0.01).

CONCLUSION: The results suggest that edaravone reduces mitochondrial damage due to reperfusion injury, resulting in a high level of glycogen storage.