Edaravone protects from memory impairment induced by chronic L-methionine administration.

Abstract

Hyperhomocysteinemia is a well-known cause of cognitive impairment and neurodegeneration. Increased oxidative stress in the brain has a major possible role in hyperhomocysteinemia-induced pathogenesis. Edaravone is a potent free radical scavenger that has a neuroprotective effect against memory impairment in several experimental models. The current study investigated the possible protective effect of edaravone in L-methionine-induced vascular dementia in a rat model. L-methionine was given (1.7 mg/kg/day) through oral gavage, while edaravone was given (6 mg/kg/day) intraperitoneally. The administration of methionine and edaravone started concomitantly and continued for a total of 9 weeks. Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in the oxidative stress-related biomarkers in the hippocampus were assessed using enzymatic assays. Chronic L-methionine administration resulted in short-term and long-term memory impairment, whereas edaravone prevented such effect. Furthermore, edaravone ameliorated L-methionine induced decrease in the activity of the antioxidant enzymes catalase and glutathione peroxidase as well as the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG ratio). Edaravone also prevented increase in the oxidized glutathione (GSSG) secondary to chronic L-methionine administration. In conclusion, the current study suggests that memory impairment and oxidative stress secondary to chronic L-methionine administration can be prevented by edaravone, probably via enhancing antioxidant mechanisms in the hippocampus.