N-acetylcysteine prevents rotenone-induced Parkinson's disease in rat: An investigation into the interaction of parkin and Drp1 proteins

Brain Res Bull. 2015 Apr;113:34-40. doi: 10.1016/j.brainresbull.2015.02.007. Epub 2015 Feb 28.

Abstract

There are convincing evidences that oxidative stress has an important role in both the initiation and progression of Parkinson's disease. N-acetylcysteine (NAC) is shown to have antioxidant properties via fortifying glutathione which is one of the main endogenous antioxidant systems. Therefore our study was aimed to evaluate the effect of NAC in management of Parkinson's disease. To this aim, male Wistar rats (10-12 months) received rotenone 2.5mg/kg/48 h intraperitoneally (ip) to induce a Parkinson's disease model. Pretreatment with NAC (25 and 50mg/kg/48 h ip) was administered 1h before the rotenone injection. Three behavioral tests (rotarod, rearing and bar tests) were performed for motor function assessment. Dopamine levels of dopaminergic areas in rat brain including substantia nigra (SN) and striatum (ST) were assessed using high performance liquid chromatography analysis to measure the loss of dopamine. Western blot analysis was also done for parkin and Drp1 (dynamin related protein-1) proteins quantification in SN and ST. Our results indicated that NAC significantly ameliorated the rotenone-induced motor dysfunction and dopamine loss. Furthermore, NAC was able to prevent the rotenone-induced changes in parkin and Drp1 levels in the both studied areas. In conclusion we found that NAC delayed the Parkinson's disease induction by rotenone and this effect might be related to its proved antioxidant effect.

Keywords: Drp1; N-acetylcysteine; Parkin; Parkinson's disease; Rotenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism
  • Drug Interactions
  • Dynamins / metabolism*
  • Male
  • Oxidative Stress / drug effects
  • Parkinsonian Disorders / chemically induced*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / prevention & control*
  • Protein Binding
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Rotarod Performance Test
  • Rotenone / antagonists & inhibitors*
  • Rotenone / pharmacology
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Rotenone
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Dnm1l protein, rat
  • Dynamins
  • Dopamine
  • Acetylcysteine