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Role of Cerium Oxide Nanoparticles in a Paraquat-Induced Model of Oxidative Stress: Emergence of Neuroprotective Results in the Brain

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Abstract

Paraquat (PQ), as a widely used herbicide, enhances the formation of free radicals and oxidative stress. Cerium oxide nanoparticles (CeNPs) are one of the most utilized and effective nanoparticles having strong antioxidative properties and inhibiting free radicals. Here, we aimed to investigate the effects of CeNPs on brain oxidative toxic stress injury induced with PQ. The male rats were treated intraperitoneally daily with PQ (50 mg/kg/day) and CeNPs (15, 30, and 60 mg/kg/day) alone or in combination for 2 weeks. After treatments, the brain tissue samples were collected. Oxidative toxic stress biomarkers including lipid peroxidation (LPO), total antioxidant capacity (TAC), and total thiol molecules (TTM) as well as DNA damage and caspase-3 levels were measured. Moreover, the mRNA expression levels of Nestin and Neurod1 were assayed. Our results showed that PQ has significantly increased brain LPO, DNA damage, and caspase-3 levels and further reduced TAC and TTM contents, as well as expression levels of Nestin and Neurod1, compared with the control group (injection of saline). CeNPs (15- and 30-mg/kg doses) in groups co-administered with PQ significantly ameliorated the LPO, DNA damage, and caspase-3 levels while increasing TAC and TTM contents as well as enhancing Nestin and Neurod1 mRNA expression levels in the brain samples (P < 0.05). These findings suggest a neuroprotective and antioxidant role for CeNPs in PQ-induced brain injury. However, further studies are required to clarify its clinical/pharmacological significance.

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References

  • Alaraby M et al (2015) Antioxidant and antigenotoxic properties of CeO2 NPs and cerium sulphate: studies with Drosophila melanogaster as a promising in vivo model. Nanotoxicology 9:749–759

    Article  CAS  Google Scholar 

  • Amirshahrokhi K, Bohlooli S (2013) Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice. Inflammation 36:1111–1121

    Article  CAS  Google Scholar 

  • Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Med Cell Longev 2014

  • Bailey ZS et al. (2016) Cerium oxide nanoparticles improve outcome after in vitro and in vivo mild traumatic brain injury. J Neurotrauma

  • Benzie IF, Strain J (1999) [2] Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. In: Methods in enzymology, vol 299. Elsevier, pp 15–27

  • Bernal A, Arranz L (2018) Nestin-expressing progenitor cells: function, identity and therapeutic implications. Cell Mol Life Sci 1–19

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  • Caputo F et al (2015) Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis. Nanoscale 7:15643–15656

    Article  CAS  Google Scholar 

  • Chen B-H, Stephen Inbaraj B (2018) Various physicochemical and surface properties controlling the bioactivity of cerium oxide nanoparticles. Crit Rev Biotechnol 1–22

  • Chen J, Patil S, Seal S, McGinnis JF (2006) Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat Nanotechnol 1:142

    Article  CAS  Google Scholar 

  • Chen J-L et al (2015) Methylene blue attenuates acute liver injury induced by paraquat in rats. Int Immunopharmacol 28:808–812

    Article  CAS  Google Scholar 

  • Colon J et al (2009) Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine 5:225–231

    Article  CAS  Google Scholar 

  • Colon J, Hsieh N, Ferguson A, Kupelian P, Seal S, Jenkins DW, Baker CH (2010) Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine 6:698–705

    Article  CAS  Google Scholar 

  • Cui D et al (2014) Effect of cerium oxide nanoparticles on asparagus lettuce cultured in an agar medium. Environ Sci Nano 1:459–465

    Article  CAS  Google Scholar 

  • Das M, Patil S, Bhargava N, Kang J-F, Riedel LM, Seal S, Hickman JJ (2007) Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 28:1918–1925

    Article  CAS  Google Scholar 

  • Erdakos GB, Bhave PV, Pouliot GA, Simon H, Mathur R (2014) Predicting the effects of nanoscale cerium additives in diesel fuel on regional-scale air quality. Environ Sci Technol 48:12775–12782

    Article  CAS  Google Scholar 

  • Estevez A et al (2011) Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic Biol Med 51:1155–1163

    Article  CAS  Google Scholar 

  • Fu X, Shen Y, Wang W, Li X (2018) MiR-30a-5p ameliorates spinal cord injury-induced inflammatory responses and oxidative stress by targeting Neurod 1 through MAPK/ERK signalling. Clin Exp Pharmacol Physiol 45:68–74

    Article  CAS  Google Scholar 

  • Gao Z et al (2009) Neurod1 is essential for the survival and maturation of adult-born neurons. Nat Neurosci 12:1090

    Article  CAS  Google Scholar 

  • Heckman KL et al (2013) Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain. ACS Nano 7:10582–10596

    Article  CAS  Google Scholar 

  • Hendrickson ML, Zutshi I, Wield A, Kalil RE (2018) Nestin expression and in vivo proliferative potential of tanycytes and ependymal cells lining the walls of the third ventricle in the adult rat brain. Eur J Neurosci 47:284–293

    Article  Google Scholar 

  • Hosseini A et al (2015) Cerium and yttrium oxide nanoparticles against lead-induced oxidative stress and apoptosis in rat hippocampus. Biol Trace Elem Res 164:80–89

    Article  CAS  Google Scholar 

  • Hu M, Dillard C (1994) Plasma SH and GSH measurement. Methods Enzymol 233:87

    Google Scholar 

  • Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39:73–82

    Article  CAS  Google Scholar 

  • Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345:91–104

    Article  CAS  Google Scholar 

  • Khanam R et al. (2018) Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation, migration and induces apoptosis in human cervical cancer HeLa cells through oxidative stress mediated intrinsic mitochondrial pathway. Apoptosis 1–19

  • Korsvik C, Patil S, Seal S, Self WT (2007) Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem Commun 1056–1058

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Ma W, Jing L, Valladares A, Mehta SL, Wang Z, Li PA, Bang JJ (2015) Silver nanoparticle exposure induced mitochondrial stress, caspase-3 activation and cell death: amelioration by sodium selenite. Int J Biol Sci 11:860

    Article  CAS  Google Scholar 

  • McCormack AL, Atienza JG, Johnston LC, Andersen JK, Vu S, Di Monte DA (2005) Role of oxidative stress in paraquat-induced dopaminergic cell degeneration. J Neurochem 93:1030–1037

    Article  CAS  Google Scholar 

  • Ming G-L, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70:687–702

    Article  CAS  Google Scholar 

  • Morán JM, Ortiz-Ortiz MA, Ruiz-Mesa LM, Fuentes JM (2010) Nitric oxide in paraquat-mediated toxicity: a review. J Biochem Mol Toxicol 24:402–409

    Article  Google Scholar 

  • Naseri S, Moghahi SMHN, Mokhtari T, Roghani M, Shirazi AR, Malek F, Rastegar T (2017) Radio-protective effects of melatonin on subventricular zone in irradiated rat: decrease in apoptosis and upregulation of Nestin. J Mol Neurosci 63:198–205

    Article  CAS  Google Scholar 

  • Nazıroğlu M, Şenol N, Ghazizadeh V, Yürüker V (2014) Neuroprotection induced by N-acetylcysteine and selenium against traumatic brain injury-induced apoptosis and calcium entry in hippocampus of rat. Cell Mol Neurobiol 34:895–903

    Article  Google Scholar 

  • Nelson BC, Johnson ME, Walker ML, Riley KR, Sims CM (2016) Antioxidant cerium oxide nanoparticles in biology and medicine. Antioxidants 5:15

    Article  Google Scholar 

  • Niu J, Azfer A, Rogers LM, Wang X, Kolattukudy PE (2007) Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res 73:549–559

    Article  CAS  Google Scholar 

  • Niu J, Wang K, Kolattukudy PE (2011) Cerium oxide nanoparticles inhibits oxidative stress and nuclear factor-κB activation in H9c2 cardiomyocytes exposed to cigarette smoke extract. J Pharmacol Exp Ther 338:53–61

    Article  CAS  Google Scholar 

  • Nunes ME et al (2017) Chronic treatment with paraquat induces brain injury, changes in antioxidant defenses system, and modulates behavioral functions in zebrafish. Mol Neurobiol 54:3925–3934

    Article  CAS  Google Scholar 

  • Oberdörster G, Elder A, Rinderknecht A (2009) Nanoparticles and the brain: cause for concern? J Nanosci Nanotechnol 9:4996–5007

    Article  Google Scholar 

  • Özel RE, Hayat A, Wallace KN, Andreescu S (2013) Effect of cerium oxide nanoparticles on intestinal serotonin in zebrafish. RSC Adv 3:15298–15309

    Article  Google Scholar 

  • Pourkhalili N et al (2011) Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. World J Diabetes 2:204

    Article  Google Scholar 

  • Rajeshkumar S, Naik P (2017) Synthesis and biomedical applications of cerium oxide nanoparticles–a review. Biotechnol Rep

  • Rzigalinski BA, Meehan K, Davis RM, Xu Y, Miles WC, Cohen CA (2006) Radical nanomedicine

  • Rzigalinski BA, Carfagna CS, Ehrich M (2017) Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 9:e1444

    Google Scholar 

  • Sadhu A, Ghosh I, Moriyasu Y, Mukherjee A, Bandyopadhyay M (2018) Role of cerium oxide nanoparticle-induced autophagy as a safeguard to exogenous H2O2-mediated DNA damage in tobacco BY-2 cells. Mutagenesis 33:161–177

    Article  Google Scholar 

  • Sahlgren CM, Pallari HM, He T, Chou YH, Goldman RD, Eriksson JE (2006) A Nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death. EMBO J 25:4808–4819

    Article  CAS  Google Scholar 

  • Tarnuzzer RW, Colon J, Patil S, Seal S (2005) Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett 5:2573–2577

    Article  CAS  Google Scholar 

  • Uittenbogaard M, Baxter KK, Chiaramello A (2010) The neurogenic basic helix-loop-helix transcription factor NeuroD6 confers tolerance to oxidative stress by triggering an antioxidant response and sustaining the mitochondrial biomass. ASN Neuro 2:AN20100005

    Article  Google Scholar 

  • Xu C, Qu X (2014) Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Mater 6:e90

    Article  CAS  Google Scholar 

  • Yagi K (1998) Simple assay for the level of total lipid peroxides in serum or plasma. In: Free radical and antioxidant protocols. Springer, pp 101–106

  • Yang B, Mei H, Zuo F, Gan L (2017) Expression of microRNAs associated with oxidative stress in the hippocampus of piglets. Genes Genomics 39:701–712

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by a grant from the Neurophysiology Research Center, Hamadan University of Medical Sciences (Grant Number, 9410015229).

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Authors and Affiliations

  1. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Akram Ranjbar & Masoumeh Taheri Azandariani

  2. Anatomy Department, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Sara Soleimani Asl

  3. Department of Pharmaceutical, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

    Farzin Firozian

  4. Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

    Hamid Heidary Dartoti & Maziar Ganji

  5. Department of Molecular Medicine and Genetic, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Saman Seyedabadi

  6. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maziar Ganji

Authors
  1. Akram Ranjbar
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  2. Sara Soleimani Asl
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  3. Farzin Firozian
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  4. Hamid Heidary Dartoti
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  5. Saman Seyedabadi
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Correspondence to Maziar Ganji.

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Ranjbar, A., Soleimani Asl, S., Firozian, F. et al. Role of Cerium Oxide Nanoparticles in a Paraquat-Induced Model of Oxidative Stress: Emergence of Neuroprotective Results in the Brain. J Mol Neurosci 66, 420–427 (2018). https://doi.org/10.1007/s12031-018-1191-2

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  • DOI: https://doi.org/10.1007/s12031-018-1191-2

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