Neuroprotective potential of atorvastatin and simvastatin (HMG-CoA reductase inhibitors) against 6-hydroxydopamine (6-OHDA) induced Parkinson-like symptoms

Brain Res. 2012 Aug 30:1471:13-22. doi: 10.1016/j.brainres.2012.06.050. Epub 2012 Jul 10.

Abstract

Neuro-inflammation and oxidative stress plays a key role in the pathophysiology of Parkinson's disease (PD). Studies demonstrated that neuro-inflammation and associated infiltration of inflammatory cells into central nervous system are inhibited by 3-hydroxy-3-methyl glutaryl co-enzyme A (HMG-CoA) reductase inhibitors. Based on these experimental evidences, the present study has been designed to evaluate the neuroprotective effect of HMG-CoA reductase inhibitors (atorvastatin and simvastatin) against 6-hydroxydopamine (6-OHDA) induced unilateral lesion model of PD. In the present study, the animals were divided into nine groups (n=15 per group). Group I: Naive (without treatment); Group II: Sham (surgery performed, vehicle administered); Group III: Atorvastatin (20mg/kg); Group IV: Simvastatin (30 mg/kg); Group V: Control [Intrastriatal 6-OHDA (20 μg; single unilateral injection)]; Groups VI and VII: 6-OHDA (20 μg)+atorvastatin (10mg/kg and 20mg/kg) respectively; Groups VIII and IX: 6-OHDA (20 μg)+simvastatin (15 mg/kg and 30 mg/kg) respectively. Intrastriatal administration of 6-OHDA (20 μg; 4 μl of 5 μg/μl) significantly caused impairment in body weight, locomotor activity, rota-rod performance, oxidative defense and mitochondrial enzyme complex activity, and increase in the inflammatory cytokine levels (TNF-α and IL-6) as compared to naive animals. Atorvastatin (20mg/kg) and simvastatin (30 mg/kg) drug treatment significantly improved these behavioral and biochemical alterations restored mitochondrial enzyme complex activities and attenuated neuroinflammatory markers in 6-OHDA (20 μg) treated animals as compared to control group. The findings of the present study demonstrate the neuroprotective potential of statins in experimental model of 6-OHDA induced Parkinson like symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine
  • Analysis of Variance
  • Animals
  • Atorvastatin
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay
  • Glutathione / metabolism
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Interleukin-6 / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Motor Activity / drug effects
  • NADH Dehydrogenase / metabolism
  • Nitrites / metabolism
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / prevention & control*
  • Pyrroles / therapeutic use*
  • Rats
  • Rats, Wistar
  • Simvastatin / therapeutic use*
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-6
  • Nitrites
  • Pyrroles
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Oxidopamine
  • Atorvastatin
  • Simvastatin
  • Amphetamine
  • NADH Dehydrogenase
  • thiazolyl blue
  • Glutathione