Neuroprotection of agomelatine against cerebral ischemia/reperfusion injury through an antiapoptotic pathway in rat
Autor: | Wijitra Chumboatong, Chainarong Tocharus, Jiraporn Tocharus, Sarinthorn Thummayot, Piyarat Govitrapong, Jinatta Jittiwat |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Agonist medicine.drug_class Ischemia Apoptosis Pharmacology Neuroprotection Antioxidants Melatonin 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Acetamides medicine Agomelatine Animals Hypnotics and Sedatives Rats Wistar TUNEL assay business.industry Brain Cell Biology medicine.disease Heme oxygenase Oxidative Stress 030104 developmental biology Anesthesia Reperfusion Injury business Reperfusion injury 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Neurochemistry international. 102 |
ISSN: | 1872-9754 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |