Abstract
BackgroundStudies 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.MethodsC57BL6 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.ResultsThis 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.ConclusionsEdaravone 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.
Highlights
Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle
The pathophysiology of I/R injuries has not been fully elucidated due to complex interactions of inflammatory and immunologic signaling pathways [8], it is clear that accumulated free radicals and anaerobic metabolites during ischemia cause the migration of white blood cells and the release of inflammatory factors such as interleukin and free radicals in the reperfusion phase [9,10,11,12,13]
There was no thrombosis in arteries and no Deep Venous Thrombosis (DVT) observed
Summary
Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The pathophysiology of I/R injuries has not been fully elucidated due to complex interactions of inflammatory and immunologic signaling pathways [8], it is clear that accumulated free radicals and anaerobic metabolites during ischemia cause the migration of white blood cells and the release of inflammatory factors such as interleukin and free radicals in the reperfusion phase [9,10,11,12,13] These compounds eventually damage muscle tissues, resulting in irrecoverable muscle damage and general complications [14,15,16]. Ozyurt et al described how caffeic acid phenethyl ester (CAPE) protected skeletal muscles from reperfusion injury, and how this protective effect can probably be ascribed to CAPE’s free radical scavenging activity [19]
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