Neuroprotective effects of three different sizes nanochelating based nano complexes in MPP(+) induced neurotoxicity

Apoptosis. 2015 Mar;20(3):298-309. doi: 10.1007/s10495-014-1069-x.

Abstract

Parkinson's disease (PD) is the world's second most common dementia, which the drugs available for its treatment have not had effects beyond slowing the disease process. Recently nanotechnology has induced the chance for designing and manufacturing new medicines for neurodegenerative disease. It is demonstrated that by tuning the size of a nanoparticle, the physiological effect of the nanoparticle can be controlled. Using novel nanochelating technology, three nano complexes: Pas (150 nm), Paf (100 nm) and Pac (40 nm) were designed and in the present study their neuroprotective effects were evaluated in PC12 cells treated with 1-methyl-4-phenyl-pyridine ion (MPP (+)). PC12 cells were pre-treated with the Pas, Paf or Pac nano complexes, then they were subjected to 10 μM MPP (+). Subsequently, cell viability, intracellular free Calcium and reactive oxygen species (ROS) levels, mitochondrial membrane potential, catalase (CAT) and superoxide dismutase (SOD) activity, Glutathione (GSH) and malondialdehyde (MDA) levels and Caspase 3 expression were evaluated. All three nano complexes, especially Pac, were able to increase cell viability, SOD and CAT activity, decreased Caspase 3 expression and prevented the generation of ROS and the loss of mitochondrial membrane potential caused by MPP(+). Pre-treatment with Pac and Paf nano complexes lead to a decrease of intracellular free Calcium, but Pas nano complex could not decrease it. Only Pac nano complex decreased MDA levels and other nano complexes could not change this parameter compared to MPP(+) treated cells. Hence according to the results, all nanochelating based nano complexes induced neuroprotective effects in an experimental model of PD, but the smallest nano complex, Pac, showed the best results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Caspase 3 / metabolism
  • Catalase / metabolism
  • Cell Survival / drug effects
  • Glutarates / chemical synthesis
  • Glutarates / pharmacology*
  • Glutathione / metabolism
  • Iron Chelating Agents / chemical synthesis
  • Iron Chelating Agents / pharmacology*
  • Malondialdehyde / antagonists & inhibitors
  • Malondialdehyde / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Piperidines / antagonists & inhibitors
  • Piperidines / pharmacology
  • Polymerization
  • Pyrazoles / antagonists & inhibitors
  • Pyrazoles / pharmacology
  • Rats
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • 1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole
  • Glutarates
  • Iron Chelating Agents
  • Neuroprotective Agents
  • Piperidines
  • Pyrazoles
  • Reactive Oxygen Species
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase
  • Caspase 3
  • Glutathione
  • glutaric acid
  • Calcium