Publication: Neuroprotection of agomelatine against cerebral ischemia/reperfusion injury through an antiapoptotic pathway in rat
Issued Date
2017-01-01
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ISSN
18729754
01970186
01970186
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2-s2.0-85007524317
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Mahidol University
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SCOPUS
Bibliographic Citation
Neurochemistry International. Vol.102, (2017), 114-122
Suggested Citation
Wijitra Chumboatong, Sarinthorn Thummayot, Piyarat Govitrapong, Chainarong Tocharus, Jinatta Jittiwat, Jiraporn Tocharus Neuroprotection of agomelatine against cerebral ischemia/reperfusion injury through an antiapoptotic pathway in rat. Neurochemistry International. Vol.102, (2017), 114-122. doi:10.1016/j.neuint.2016.12.011 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42066
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Title
Neuroprotection of agomelatine against cerebral ischemia/reperfusion injury through an antiapoptotic pathway in rat
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Abstract
© 2016 Elsevier Ltd Agomelatine is an agonist of the melatonergic MT1/MT2 receptors and an antagonist of the serotonergic 5-HT receptors. Its actions mimic melatonin in antioxidative and anti-inflammation. However, the protective mechanism of agomelatine in ischemic/reperfusion (I/R) injury has not been investigated. In this study, cerebral I/R injury rats were induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The rats were randomly divided into 6 groups (12 rats per group): sham-operated; vehicle-treated I/R; 20 mg/kg, 40 mg/kg, and 80 mg/kg agomelatine-treated I/R; and 10 mg/kg melatonin-treated I/R. Agomelatine and melatonin were intraperitoneally administrated to the rats 1 h before MCAO induction. After reperfusion for 24 h, the brain samples were harvested for evaluating the infarct volume, histological changes, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining as well as cleaved caspase-3, Bax, Bcl-XL, nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase (HO-1) levels. Agomelatine treatment significantly decreased apoptosis, with decreases in Bax and cleaved caspase-3, and increased Bcl-XL, along with a decrease in apoptotic neuronal cells. Moreover, agomelatine was also found to markedly increase the expression of HO-1, the antioxidative enzymes, and the activity of superoxide dismutase (SOD) mediated by Nrf2 pathway. Agomelatine treatment protects the brain from cerebral I/R injury by suppressing apoptosis and agomelatine has antioxidant properties. Hence, there exists the possibility of developing agomelatine as a potential candidate for treating ischemic stroke.