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.
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Deanship of Research/Jordan University of Science and Technology, grant number 522/2018.
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KA and FM conceived and designed research. ZA conducted experiments. KA and FM contributed new reagents, analytical tools, and in supervising the experimental procedure. KA and ZA analyzed data. KA, ZA, and FM participated in interpreting study results and wrote the manuscript. All authors read and approved the manuscript.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The experimental protocol was approved by the animal care and use committee (ACUC) of the Jordan University of Science and Technology (approval number: IACUC-522/2018, 25-11-2018).
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Alzoubi, K.H., Aburashed, Z.O. & Mayyas, F. Edaravone protects from memory impairment induced by chronic L-methionine administration. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1221–1228 (2020). https://doi.org/10.1007/s00210-020-01827-z
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DOI: https://doi.org/10.1007/s00210-020-01827-z