O. Abdel-Salam, A. Sleem, E. Youness, N. Mohammed, E. Omara, Marwa E. Shabana
{"title":"Neuroprotective Effects of the Glutathione Precursor N-Acetylcysteine against Rotenone-Induced Neurodegeneration","authors":"O. Abdel-Salam, A. Sleem, E. Youness, N. Mohammed, E. Omara, Marwa E. Shabana","doi":"10.20455/ROS.2019.845","DOIUrl":null,"url":null,"abstract":"In this study, the neuroprotective potential of the glutathione precursor N-acetylcysteine in the rotenone-induced Parkinson’s disease (PD) was investigated. Rats were administered rotenone (1.5 mg/kg/day) once every other day for 2 weeks by subcutaneous injection. Starting from the first day of rotenone treatment, rats received the vehicle control or N-acetylcysteine (NAC) at doses of 10 and 30 mg/kg orally given at time of rotenone injection. Rats were evaluated for brain malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide content, and paraoxonase-1 (PON-1) activity in the striatum, cerebral cortex, and the rest of the brain tissue. The level of the anti-apoptotic Bcl-2 was also determined in the striatum. In addition, histopathological examination and the expression of cycloxygenase-2 (COX-2) in the striatum and cerebral cortex were performed. Rotenone treatment caused a significant increase in MDA and nitric acid content in the striatum, cerebral cortex, and the rest of the brain tissue. It also significantly decreased brain GSH content and PON-1 activity in these regions and decreased striatal Bcl-2 level compared to control values. Rotenone treatment caused neuronal necrosis, apoptosis, and vacuolization, and increased the expression of COX-2 in both the striatum and cerebral cortex. NAC given at doses of 10 and 30 mg/kg to rotenone-treated rats caused a dose-dependent significant decrease in MDA levels in the cortex and the rest of the brain tissue and at the dose of 30 mg/kg significantly decreased the striatal MDA level. It also significantly decreased the nitric oxide level, increased GSH content and PON-1 activity in the striatum, cerebral cortex, and the rest of the brain when given at doses of 10 and 30 mg/kg. Additionally, there was a significant increase in the striatal Bcl-2 level by NAC at 30 mg/kg. NAC decreased neuronal necrosis and apoptosis as well as COX-2 immunostaining in both the striatum and cerebral cortex in a dose-dependent manner. These findings suggest a potential benefit for NAC in alleviating brain oxidative stress, neuroinflammation, and neurodegeneration in the rotenone model of PD in rats. NAC could thus be a useful adjunct in the treatment of patients with PD.","PeriodicalId":91793,"journal":{"name":"Reactive oxygen species (Apex, N.C.)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"7","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reactive oxygen species (Apex, N.C.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.20455/ROS.2019.845","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 7
Abstract
In this study, the neuroprotective potential of the glutathione precursor N-acetylcysteine in the rotenone-induced Parkinson’s disease (PD) was investigated. Rats were administered rotenone (1.5 mg/kg/day) once every other day for 2 weeks by subcutaneous injection. Starting from the first day of rotenone treatment, rats received the vehicle control or N-acetylcysteine (NAC) at doses of 10 and 30 mg/kg orally given at time of rotenone injection. Rats were evaluated for brain malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide content, and paraoxonase-1 (PON-1) activity in the striatum, cerebral cortex, and the rest of the brain tissue. The level of the anti-apoptotic Bcl-2 was also determined in the striatum. In addition, histopathological examination and the expression of cycloxygenase-2 (COX-2) in the striatum and cerebral cortex were performed. Rotenone treatment caused a significant increase in MDA and nitric acid content in the striatum, cerebral cortex, and the rest of the brain tissue. It also significantly decreased brain GSH content and PON-1 activity in these regions and decreased striatal Bcl-2 level compared to control values. Rotenone treatment caused neuronal necrosis, apoptosis, and vacuolization, and increased the expression of COX-2 in both the striatum and cerebral cortex. NAC given at doses of 10 and 30 mg/kg to rotenone-treated rats caused a dose-dependent significant decrease in MDA levels in the cortex and the rest of the brain tissue and at the dose of 30 mg/kg significantly decreased the striatal MDA level. It also significantly decreased the nitric oxide level, increased GSH content and PON-1 activity in the striatum, cerebral cortex, and the rest of the brain when given at doses of 10 and 30 mg/kg. Additionally, there was a significant increase in the striatal Bcl-2 level by NAC at 30 mg/kg. NAC decreased neuronal necrosis and apoptosis as well as COX-2 immunostaining in both the striatum and cerebral cortex in a dose-dependent manner. These findings suggest a potential benefit for NAC in alleviating brain oxidative stress, neuroinflammation, and neurodegeneration in the rotenone model of PD in rats. NAC could thus be a useful adjunct in the treatment of patients with PD.