Neuroprotective Effects of the Glutathione Precursor N-Acetylcysteine against Rotenone-Induced Neurodegeneration

  • Omar M.E. Abdel-Salam Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt
  • Amany A. Sleem Department of Pharmacology, National Research Centre, Cairo, Egypt
  • Eman R. Youness Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
  • Nadia A. Mohammed Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
  • Enayat A. Omara Department of Pathology, National Research Centre, Cairo, Egypt
  • Marwa E. Shabana Department of Pathology, National Research Centre, Cairo, Egypt
Keywords: N-Acetylcysteine; Bcl-2; Cyclooxygenase; Glutathione; Malondialdehyde; Neurodegeneration; Neuroprotection; Nitric oxide; Paraoxonase; Parkinson’s disease; Rotenone

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.

Published
2019-07-01
How to Cite
Abdel-Salam, O. M., Sleem, A. A., Youness, E. R., Mohammed, N. A., Omara, E. A., & Shabana, M. E. (2019). Neuroprotective Effects of the Glutathione Precursor N-Acetylcysteine against Rotenone-Induced Neurodegeneration. Reactive Oxygen Species, 8(22), 231–244. Retrieved from https://www.aimsci.com/ros/index.php/ros/article/view/216
Section
Original Research Articles