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

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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.

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References

  1. Youdim MB, Buccafusco JJ (2005) CNS Targets for multi-functional drugs in the treatment of Alzheimer’s and Parkinson’s diseases. J Neural Transm 112:519–537

    Article  CAS  PubMed  Google Scholar 

  2. Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1:120–129

    Article  CAS  PubMed  Google Scholar 

  3. Connor JR, Menzies SL, Burdo JR, Boyer PJ (2001) Iron and iron management proteins in neurobiology. Pediatr Neurol 25:118–129

    Article  CAS  PubMed  Google Scholar 

  4. Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Med 10(Suppl):S10–S17

    Article  PubMed  Google Scholar 

  5. Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Arundine M, Tymianski M (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34:325–337

    Article  CAS  PubMed  Google Scholar 

  7. Saini R, Saini S, Sharma S (2010) Nanotechnology: the future medicine. J Cutan Aesthetic Surg 3:32–33

    Article  Google Scholar 

  8. Silva GA (2008) Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS. BMC Neurosci 9(Suppl 3):S4

    Article  PubMed Central  PubMed  Google Scholar 

  9. Liu Y, Tan J, Thomas A, Ou-Yang D, Muzykantov VR (2012) The shape of things to come: importance of design in nanotechnology for drug delivery. Therapeutic Deliv 3:181–194

    Article  CAS  Google Scholar 

  10. Fakharzadeh S, Kalanaky S, Hafizi M et al (2013) The new nano-complex, Hep-c, improves the immunogenicity of the hepatitis B vaccine. Vaccine 31:2591–2597

    Article  CAS  PubMed  Google Scholar 

  11. Fakharzadeh S, Sahraian MA, Hafizi M et al (2014) The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice. Int J Nanomedicine 9:3841–3853

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Youdim MB (2013) Multi target neuroprotective and neurorestorative anti-Parkinson and anti-Alzheimer drugs ladostigil and m30 derived from rasagiline. Exp Neurobiol 22:1–10

    Article  PubMed Central  PubMed  Google Scholar 

  13. Sian-Hulsmann J, Mandel S, Youdim MB, Riederer P (2011) The relevance of iron in the pathogenesis of Parkinson’s disease. J Neurochem 118:939–957

    Article  PubMed  Google Scholar 

  14. Weinreb O, Mandel S, Youdim MB, Amit T (2013) Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators. Free Radic Biol Med 62:52–64

    Article  CAS  PubMed  Google Scholar 

  15. Blum D, Torch S, Lambeng N et al (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 65:135–172

    Article  CAS  PubMed  Google Scholar 

  16. Nazaran MH (2012) Chelate compounds. Google Patents

  17. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    Article  CAS  PubMed  Google Scholar 

  18. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  19. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  20. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132

    CAS  PubMed  Google Scholar 

  21. Pelicano H, Feng L, Zhou Y et al (2003) Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. J Biol Chem 278:37832–37839

    Article  CAS  PubMed  Google Scholar 

  22. Kim I, Xu W, Reed JC (2008) Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discovery 7:1013–1030

    Article  CAS  Google Scholar 

  23. Nicholson DW, Ali A, Thornberry NA et al (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43

    Article  CAS  PubMed  Google Scholar 

  24. Baba A, Onoe H, Ohta A, Iwata H (1986) Assay of phospholipase A2 activity of synaptic membranes using a phospholipid transfer protein: stimulation by depolarization. Biochim Biophys Acta 878:25–31

    Article  CAS  PubMed  Google Scholar 

  25. Potter TM, Neun BW, Stern ST (2011) Assay to detect lipid peroxidation upon exposure to nanoparticles. Methods Mol Biol 697:181–189

    Article  CAS  PubMed  Google Scholar 

  26. Chrobot AM, Szaflarska-Szczepanik A, Drewa G (2000) Antioxidant defense in children with chronic viral hepatitis B and C. Med Sci Monit 6:713–718

    CAS  PubMed  Google Scholar 

  27. Venardos K, Harrison G, Headrick J, Perkins A (2004) Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia-reperfusion. J Trace Elem Med Biol 18:81–88

    Article  CAS  PubMed  Google Scholar 

  28. Tatton WG, Chalmers-Redman R, Brown D, Tatton N (2003) Apoptosis in Parkinson’s disease: signals for neuronal degradation. Ann Neurol 53(Suppl 3):S61–70; discussion S70–62

  29. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331

    Article  CAS  PubMed  Google Scholar 

  30. Green DR (2000) Apoptotic pathways: paper wraps stone blunts scissors. Cell 102:1–4

    Article  CAS  PubMed  Google Scholar 

  31. Berg D, Youdim MB (2006) Role of iron in neurodegenerative disorders. Top Magn Resonance Imaging 17:5–17

    Article  Google Scholar 

  32. Riederer PYM (1993) Iron in central nervous system disorders. Springer, Wien, pp 189–196

    Book  Google Scholar 

  33. Richardson DR (2004) Novel chelators for central nervous system disorders that involve alterations in the metabolism of iron and other metal ions. Ann N Y Acad Sci 1012:326–341

    Article  CAS  PubMed  Google Scholar 

  34. Floor E (2000) Iron as a vulnerability factor in nigrostriatal degeneration in aging and Parkinson’s disease. Cell Mol Biol (Noisy-le-grand) 46:709–720

    CAS  Google Scholar 

  35. Blake DR, Winyard P, Lunec J et al (1985) Cerebral and ocular toxicity induced by desferrioxamine. Q J Med 56:345–355

    CAS  PubMed  Google Scholar 

  36. Kruck TP, Fisher EA, McLachlan DR (1993) A predictor for side effects in patients with Alzheimer’s disease treated with deferoxamine mesylate. Clin Pharmacol Ther 53:30–37

    Article  CAS  PubMed  Google Scholar 

  37. Sahni JK, Doggui S, Ali J, Baboota S, Dao L, Ramassamy C (2011) Neurotherapeutic applications of nanoparticles in Alzheimer’s disease. J Control Release 152:208–231

    Article  CAS  PubMed  Google Scholar 

  38. Liu G, Men P, Kudo W, Perry G, Smith MA (2009) Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease. Neurosci Lett 455:187–190

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Jacotot E, Costantini P, Laboureau E, Zamzami N, Susin SA, Kroemer G (1999) Mitochondrial membrane permeabilization during the apoptotic process. Ann N Y Acad Sci 887:18–30

    Article  CAS  PubMed  Google Scholar 

  40. Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802:396–405

    Article  CAS  PubMed  Google Scholar 

  41. Li G, Ma R, Huang C et al (2008) Protective effect of erythropoietin on beta-amyloid-induced PC12 cell death through antioxidant mechanisms. Neurosci Lett 442:143–147

    Article  CAS  PubMed  Google Scholar 

  42. Tusi SK, Khalaj L, Ashabi G, Kiaei M, Khodagholi F (2011) Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress. Biomaterials 32:5438–5458

    Article  CAS  PubMed  Google Scholar 

  43. Narayanan KB, Park HH (2013) Pleiotropic functions of antioxidant nanoparticles for longevity and medicine. Adv Colloid Interface Sci 201–202:30–42

    Article  PubMed  Google Scholar 

  44. Hussain S, Garantziotis S, Rodrigues-Lima F, Dupret JM, Baeza-Squiban A, Boland S (2014) Intracellular signal modulation by nanomaterials. Adv Exp Med Biol 811:111–134

    Article  PubMed  Google Scholar 

  45. Napierska D, Thomassen LC, Rabolli V et al (2009) Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 5:846–853

    Article  CAS  PubMed  Google Scholar 

  46. Stoeger T, Reinhard C, Takenaka S et al (2006) Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. Environ Health Perspect 114:328–333

    Article  PubMed Central  PubMed  Google Scholar 

  47. Zhang FWP, Koberstein J, Khalid S, Chan SW (2004) Cerium oxidation state in ceria nanoparticles studied with X-ray photoelectron spectroscopy and absorption near edge spectroscopy. Surf Sci 563:1–3

    Article  Google Scholar 

  48. Lee SS, Song W, Cho M et al (2013) Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating. ACS Nano 7:9693–9703

    Article  CAS  PubMed  Google Scholar 

  49. Das S, Singh S, Dowding JM et al (2012) The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials 33:7746–7755

    Article  CAS  PubMed  Google Scholar 

  50. Robinson RDSJ, Zhang F, Chan SW, Herman IP (2002) Visible thermal emission from sub-band-gap laser excited cerium dioxide particles. J Appl Phys 92(4):1936–1941

    Article  CAS  Google Scholar 

  51. Neeraj Singh EA, James E Mahaney, Kathleen Meehan and Beverly A Rzigalinski. The Antioxidant Activity of Cerium Oxide Nanoparticles is Size Dependant and Blocks Aβ1-42-Induced Free Radical Production and Neurotoxicity

  52. Wiesenthal A, Hunter L, Wang S, Wickliffe J, Wilkerson M (2011) Nanoparticles: small and mighty. Int J Dermatol 50:247–254

    Article  CAS  PubMed  Google Scholar 

  53. Zhu M, Nie G, Meng H, Xia T, Nel A, Zhao Y (2013) Physicochemical properties determine nanomaterial cellular uptake, transport, and fate. Acc Chem Res 46:622–631

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Support for this work was provided by the Department of Research and Development at Sodour Ahrar Shargh Company and we are grateful to Dr Nader Maghsoudi President of Iranian Cell Death Association and Professor in Neuroscience Research Center of Shahid Beheshti University of Medical Sciences for his help in this project.

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Authors and Affiliations

  1. Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran

    Amirhossein Maghsoudi, Saideh Fakharzadeh, Maryam Hafizi, Maryam Abbasi, Fatemeh Kohram, Somayeh Kalanaky & Mohammad Hassan Nazaran

  2. Biology Department, University of Tehran, Tehran, Iran

    Amirhossein Maghsoudi & Shima Sardab

  3. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maryam Abbasi

  4. Food and Drug Office, Tehran University of Medical Sciences, Tehran, Iran

    Abbas Tahzibi

Authors
  1. Amirhossein Maghsoudi
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  2. Saideh Fakharzadeh
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  3. Maryam Hafizi
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  4. Maryam Abbasi
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  5. Fatemeh Kohram
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  6. Shima Sardab
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  7. Abbas Tahzibi
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  8. Somayeh Kalanaky
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  9. Mohammad Hassan Nazaran
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Corresponding authors

Correspondence to Somayeh Kalanaky or Mohammad Hassan Nazaran.

Additional information

M. H. Nazaran is the owner of Nanochelating Technology and executive manager and chairman of the management board of Sodour Ahrar Shargh company.

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Maghsoudi, A., Fakharzadeh, S., Hafizi, M. et al. Neuroprotective effects of three different sizes nanochelating based nano complexes in MPP(+) induced neurotoxicity. Apoptosis 20, 298–309 (2015). https://doi.org/10.1007/s10495-014-1069-x

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