Abstract
Abstract: :
Purpose: The effects of edaravone (3–methyl–1–phenyl–2–pyrazolin–5–one), a novel free radical scavenger have been found in brain ischemia, model of cochlear ischemia, acute liver injury and pancreatitis. In this study, we evaluated the efficacy of edaravone on retinal ganglion cell (RGC) degeneration may occur due to neurotoxicity of reactive oxygen species (ROS) in rat retinal ischemia/reperfusion injury. Methods: Retinal ischemia in Wistar rats was produced by transient elevation of intraocular pressure by intraocular cannulation (>110mmHg 75min). The effect of edaravone was investigated on four injection routes, intravenous (3mg/kg x3), intraperitoneal (3mg/kg x3), intravitreous (1mg/kg x9), and eye drop (1mg/kg x9) within 24h after ischemia. The dose response (0.3, 1, 3, 6, 10, 30 mg/kg x3) and timing of injection (0, 12, 24, 48, 72, 144h after ischemia) of edaravone was also examined. Aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase, was injected intraperitonealy after ischemia (3mg/kg/day) in two groups. One for injecting only acute phase (0, 1, 2 days after ischemia) and the other one for entire phase. After 1–week reperfusion, loss of RGCs was determined quantitatively by retrograde labeling with Fluoro–Gold. Results: Following ischemia/reperfusion injury, treatment with edaravone significantly reduced the loss of RGCs dose dependently up to 6mg/kg x3. Edaravone injection did not affect afterward 48h reperfusion. The neuroprotective effects were found in groups of intravitreous injection (12% cell loss in central retina, p<0.01), intravenous injection (19% cell loss, p<0.05), and intraperitoneal injection (21% cell loss, p<0.05), compared with control groups (28% cell loss). However, there is no effect with eye drop group (25% cell loss). In compare with edaravone to AG injected only acute phase, edaravone protect RGCs more than AG. Edaravone+AG group had most intensive effect (8% cell loss) compared with edaravone only group (19% cell loss) and AG only in entire phase group (13% cell loss). Conclusions: Edaravone has neuroprotective effect within 48h reperfusion, stronger than AG. ROS play more important role in acute phase of RGCs degeneration following retinal ischemia/reperfusion injury in rat.
Keywords: neuroprotection • antioxidants • nitric oxide