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Molecular Neurobiology

, Volume 56, Issue 2, pp 1221–1232 | Cite as

(E)-Nicotinaldehyde O-Cinnamyloxime, a Nicotine Analog, Attenuates Neuronal Cells Death Against Rotenone-Induced Neurotoxicity

  • Juan Camilo Jurado-Coronel
  • Alix E. Loaiza
  • John E. Díaz
  • Ricardo Cabezas
  • Ghulam Md Ashraf
  • Amirhossein Sahebkar
  • Valentina Echeverria
  • Janneth GonzálezEmail author
  • George E. BarretoEmail author
Article

Abstract

Parkinson’s disease (PD) is a neurodegenerative pathology characterized by resting tremor, rigidity, bradykinesia, and loss of dopamine-producing neurons in the pars compacta of the substantia nigra in the central nervous system (CNS) that result in dopamine depletion in the striatum. Oxidative stress has been documented as a key pathological mechanism for PD. Epidemiological studies have shown that smokers have a lower incidence of PD. In this aspect, different studies have shown that nicotine, a chemical compound found in cigarette, is capable of exerting beneficial effects in PD patients, but it can hardly be used as a therapeutic agent because of its inherent toxicity. Several studies have suggested that the use of nicotine analogs can have the same benefits as nicotine but lack its toxicity. In this study, we assessed the effects of two nicotine analogs, (E)-nicotinaldehyde O-cinnamyloxime and 3-(pyridin-3-yl)-3a,4,5,6,7,7a-hexahidrobenzo[d]isoxazole, in an in vitro model of PD. Initially, we performed a computational prediction of the molecular interactions between the nicotine analogs with the α7 nicotinic acetylcholine receptor (nAChR). Furthermore, we evaluated the effect of nicotine, nicotine analogs and rotenone on cell viability and reactive oxygen species (ROS) production in the SH-SY5Y neuronal cell line to validate possible protective effects. We observed that pre-treatment with nicotine or (E)-nicotinaldehyde O-cinnamyloxime (10 μM) improved cell viability and diminished ROS production in SH-SY5Y cells insulted with rotenone. These findings suggest that nicotine analogs have a potential protective effect against oxidative damage in brain pathologies.

Keywords

Parkinson’s disease Nicotine analogs (E)-nicotinaldehyde O-cinnamyloxime Rotenone Cell viability Oxidative stress 

Notes

Acknowledgments

This work was supported by Pontificia Universidad Javeriana (PUJ grants # 6337 and 6701) to GEB.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2018_1163_MOESM1_ESM.docx (2.8 mb)
ESM 1 (DOCX 2895 kb)

References

  1. 1.
    Kim HJ, Park HJ, Park HK, Chung JH (2009) Tranexamic acid protects against rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Toxicology 262(2):171–174PubMedCrossRefGoogle Scholar
  2. 2.
    Barreto GE, Iarkov A, Moran VE (2014) Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinson's disease. Front Aging Neurosci 6:340PubMedGoogle Scholar
  3. 3.
    Barreto GE, Yarkov A, Avila-Rodriguez M, Aliev G, Echeverria V (2015) Nicotine-derived compounds as therapeutic tools against post-traumatic stress disorder. Curr Pharm Des 21(25):3589–3595PubMedCrossRefGoogle Scholar
  4. 4.
    Echeverria V, Grizzell JA, Barreto GE (2016a) Neuroinflammation: A therapeutic target of cotinine for the treatment of psychiatric disorders? Curr Pharm Des 22(10):1324–1333PubMedCrossRefGoogle Scholar
  5. 5.
    Echeverria V, Yarkov A, Aliev G (2016b) Positive modulators of the alpha7 nicotinic receptor against neuroinflammation and cognitive impairment in Alzheimer's disease. Prog Neurobiol 144:142–157PubMedCrossRefGoogle Scholar
  6. 6.
    Grizzell JA, Patel S, Barreto GE, Echeverria V (2017) Cotinine improves visual recognition memory and decreases cortical tau phosphorylation in the Tg6799 mice. Prog Neuro-Psychopharmacol Biol Psychiatry 78:75–81CrossRefGoogle Scholar
  7. 7.
    Jurado-Coronel JC, Avila-Rodriguez M, Capani F, Gonzalez J, Moran VE, Barreto GE (2016) Targeting the nicotinic acetylcholine receptors (nAChRs) in astrocytes as a potential therapeutic target in Parkinson's disease. Curr Pharm Des 22(10):1305–1311PubMedCrossRefGoogle Scholar
  8. 8.
    Mendoza C, Barreto GE, Iarkov A, Tarasov VV, Aliev G, Echeverria V (2018) Cotinine: A therapy for memory extinction in post-traumatic stress disorder. Mol NeurobiolGoogle Scholar
  9. 9.
    Perez-Urrutia N, Mendoza C, Alvarez-Ricartes N, Oliveros-Matus P, Echeverria F, Grizzell JA, Barreto GE, Iarkov A et al (2017) Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice. Exp Neurol 295:211–221PubMedCrossRefGoogle Scholar
  10. 10.
    Ye SQ, Zhou XY, Lai XJ, Zheng L, Chen XQ (2009) Silencing neuroglobin enhances neuronal vulnerability to oxidative injury by down-regulating 14-3-3gamma. Acta Pharmacol Sin 30(7):913–918PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Quik M, Huang LZ, Parameswaran N, Bordia T, Campos C, Perez XA (2009) Multiple roles for nicotine in Parkinson's disease. Biochem Pharmacol 78(7):677–685PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Ward RJ, Lallemand F, de Witte P, Dexter DT (2008) Neurochemical pathways involved in the protective effects of nicotine and ethanol in preventing the development of Parkinson's disease: Potential targets for the development of new therapeutic agents. Prog Neurobiol 85(2):135–147PubMedCrossRefGoogle Scholar
  13. 13.
    Benowitz NL (2009) Pharmacology of nicotine: Addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 49:57–71PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Bolchi C, Valoti E, Gotti C, Fasoli F, Ruggeri P, Fumagalli L, Binda M, Mucchietto V et al (2015) Chemistry and pharmacology of a series of Unichiral analogues of 2-(2-Pyrrolidinyl)-1,4-benzodioxane, Prolinol phenyl ether, and Prolinol 3-Pyridyl ether designed as alpha4beta2-nicotinic acetylcholine receptor agonists. J Med Chem 58(16):6665–6677PubMedCrossRefGoogle Scholar
  15. 15.
    Deng CB, Li J, Li LY, Sun FJ (2016) Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase. Bioorg Med Chem Lett 26(13):3195–3201PubMedCrossRefGoogle Scholar
  16. 16.
    Pogocki D, Ruman T, Danilczuk M, Danilczuk M, Celuch M, Walajtys-Rode E (2007) Application of nicotine enantiomers, derivatives and analogues in therapy of neurodegenerative disorders. Eur J Pharmacol 563(1–3):18–39PubMedCrossRefGoogle Scholar
  17. 17.
    Rao TS, Sacaan AI, Menzaghi FM, Reid RT, Adams PB, Correa LD, Whelan KT, Vernier JM (2004) Pharmacological characterization of SIB-1663, a conformationally rigid analog of nicotine. Brain Res 1003(1–2):42–53PubMedCrossRefGoogle Scholar
  18. 18.
    Wang J, Li X, Yuan Q, Ren J, Huang J, Zeng B (2012) Synthesis and pharmacological properties of 5-alkyl substituted nicotine analogs. Chin J Chem 30(12):2813–2818CrossRefGoogle Scholar
  19. 19.
    Albarracin SL, Stab B, Casas Z, Sutachan JJ, Samudio I, Gonzalez J, Gonzalo L, Capani F et al (2012) Effects of natural antioxidants in neurodegenerative disease. Nutr Neurosci 15(1):1–9PubMedCrossRefGoogle Scholar
  20. 20.
    Mazo NA, Echeverria V, Cabezas R, Avila-Rodriguez M, Tarasov VV, Yarla NS, Aliev G, Barreto GE (2017) Medicinal plants as protective strategies against Parkinson's disease. Curr Pharm Des 23(28):4180–4188PubMedCrossRefGoogle Scholar
  21. 21.
    Sutachan JJ, Casas Z, Albarracin SL, Stab BR 2nd, Samudio I, Gonzalez J, Morales L, Barreto GE (2012) Cellular and molecular mechanisms of antioxidants in Parkinson's disease. Nutr Neurosci 15(3):120–126PubMedCrossRefGoogle Scholar
  22. 22.
    Guo L, Li L, Wang W, Pan Z, Zhou Q, Wu Z (2012) Mitochondrial reactive oxygen species mediates nicotine-induced hypoxia-inducible factor-1alpha expression in human non-small cell lung cancer cells. Biochim Biophys Acta 1822(6):852–861PubMedCrossRefGoogle Scholar
  23. 23.
    Ross GW, Petrovitch H (2001) Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. Drugs Aging 18(11):797–806PubMedCrossRefGoogle Scholar
  24. 24.
    Cabezas R, Avila MF, Gonzalez J, El-Bacha RS, Barreto GE (2015) PDGF-BB protects mitochondria from rotenone in T98G cells. Neurotox Res 27(4):355–367PubMedCrossRefGoogle Scholar
  25. 25.
    Cabezas R, El-Bacha RS, Gonzalez J, Barreto GE (2012) Mitochondrial functions in astrocytes: Neuroprotective implications from oxidative damage by rotenone. Neurosci Res 74(2):80–90PubMedCrossRefGoogle Scholar
  26. 26.
    Cabezas R, Vega-Vela NE, Gonzalez-Sanmiguel J, Gonzalez J, Esquinas P, Echeverria V, Barreto GE (2018) PDGF-BB preserves mitochondrial morphology, attenuates ROS production, and upregulates Neuroglobin in an astrocytic model under rotenone insult. Mol Neurobiol 55(4):3085–3095PubMedCrossRefGoogle Scholar
  27. 27.
    Chung WG, Miranda CL, Maier CS (2007) Epigallocatechin gallate (EGCG) potentiates the cytotoxicity of rotenone in neuroblastoma SH-SY5Y cells. Brain Res 1176:133–142PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    de Oliveira DM, Barreto G, Galeano P, Romero JI, Holubiec MI, Badorrey MS, Capani F, Alvarez LD (2011) Paullinia cupana Mart. Var. Sorbilis protects human dopaminergic neuroblastoma SH-SY5Y cell line against rotenone-induced cytotoxicity. Hum Exp Toxicol 30(9):1382–1391PubMedCrossRefGoogle Scholar
  29. 29.
    de Oliveria DM, Barreto G, De Andrade DV, Saraceno E, Aon-Bertolino L, Capani F, Dos Santos El Bacha R, Giraldez LD (2009) Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease. Neurochem Res 34(2):215–220PubMedCrossRefGoogle Scholar
  30. 30.
    Valverde GDAD, Madureira de Oliveria D, Barreto G, Bertolino LA, Saraceno E, Capani F, Giraldez LD (2008) Effects of the extract of Anemopaegma mirandum (Catuaba) on rotenone-induced apoptosis in human neuroblastomas SH-SY5Y cells. Brain Res 1198:188–196CrossRefGoogle Scholar
  31. 31.
    Li SX, Huang S, Bren N, Noridomi K, Dellisanti CD, Sine SM, Chen L (2011) Ligand-binding domain of an alpha7-nicotinic receptor chimera and its complex with agonist. Nat Neurosci 14(10):1253–1259PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Yuan H, Petukhov PA (2006) Computational evidence for the ligand selectivity to the alpha4beta2 and alpha3beta4 nicotinic acetylcholine receptors. Bioorg Med Chem 14(23):7936–7942PubMedCrossRefGoogle Scholar
  33. 33.
    Trott O, Olson AJ (2010) AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2):455–461PubMedCentralPubMedGoogle Scholar
  34. 34.
    Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19(14):1639–1662CrossRefGoogle Scholar
  35. 35.
    Diaz-Velandia J, Durán-Díaz N, Robles-Camargo J, Loaiza A (2011) Synthesis and in vitro assessment of antifungal activity of oximes, oxime ethers and isoxazoles. Univ Sci 16(3):294–302CrossRefGoogle Scholar
  36. 36.
    Minton AP (2001) The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J Biol Chem 276(14):10577–10580PubMedCrossRefGoogle Scholar
  37. 37.
    Zhou HX, Rivas G, Minton AP (2008) Macromolecular crowding and confinement: Biochemical, biophysical, and potential physiological consequences. Annu Rev Biophys 37:375–397PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Cormier A, Morin C, Zini R, Tillement JP, Lagrue G (2003) Nicotine protects rat brain mitochondria against experimental injuries. Neuropharmacology 44(5):642–652PubMedCrossRefGoogle Scholar
  39. 39.
    Prendergast MA, Harris BR, Mayer S, Littleton JM (2000) Chronic, but not acute, nicotine exposure attenuates ethanol withdrawal-induced hippocampal damage in vitro. Alcohol Clin Exp Res 24(10):1583–1592PubMedCrossRefGoogle Scholar
  40. 40.
    Noha SM, Schmidhammer H, Spetea M (2017) Molecular docking, molecular dynamics, and structure-activity relationship explorations of 14-oxygenated N-Methylmorphinan-6-ones as potent mu-opioid receptor agonists. ACS Chem Neurosci 8(6):1327–1337PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Shrivastava A, Kumar K, Prasad K (2017) Molecular docking studies: The success should overrule the doubts? Journal of Proteomics & Bioinformatics 10:202–206Google Scholar
  42. 42.
    Dukat M, Damaj IM, Young R, Vann R, Collins AC, Marks MJ, Martin BR, Glennon RA (2002) Functional diversity among 5-substituted nicotine analogs; in vitro and in vivo investigations. Eur J Pharmacol 435(2–3):171–180PubMedCrossRefGoogle Scholar
  43. 43.
    Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3(12):1301–1306CrossRefPubMedGoogle Scholar
  44. 44.
    Douna H, Bavelaar BM, Pellikaan H, Olivier B, Pieters T (2012) Neuroprotection in Parkinson’s disease: A systematic review of the preclinical data. The Open Pharmacology Journal 6(1):12–26CrossRefGoogle Scholar
  45. 45.
    Riveles K, Huang LZ, Quik M (2008) Cigarette smoke, nicotine and cotinine protect against 6-hydroxydopamine-induced toxicity in SH-SY5Y cells. Neurotoxicology 29(3):421–427PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Nakamura K, Kitamura Y, Tsuchiya D, Inden M, Taniguchi T (2004) In vitro neurodegeneration model: Dopaminergic toxin-induced apoptosis in human SH-SY5Y cells. Int Congr Ser 1260(1):287–290CrossRefGoogle Scholar
  47. 47.
    Peng J, Liu Q, Rao MS, Zeng X (2013) Using human pluripotent stem cell-derived dopaminergic neurons to evaluate candidate Parkinson's disease therapeutic agents in MPP+ and rotenone models. J Biomol Screen 18(5):522–533PubMedCrossRefGoogle Scholar
  48. 48.
    Quik M, O'Neill M, Perez XA (2007) Nicotine neuroprotection against nigrostriatal damage: Importance of the animal model. Trends Pharmacol Sci 28(5):229–235PubMedCrossRefGoogle Scholar
  49. 49.
    Takeuchi H, Yanagida T, Inden M, Takata K, Kitamura Y, Yamakawa K, Sawada H, Izumi Y et al (2009) Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models. J Neurosci Res 87(2):576–585PubMedCrossRefGoogle Scholar
  50. 50.
    Quik M, Bordia T, O'Leary K (2007) Nicotinic receptors as CNS targets for Parkinson's disease. Biochem Pharmacol 74(8):1224–1234PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Shimohama S (2009) Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models. Biol Pharm Bull 32(3):332–336PubMedCrossRefGoogle Scholar
  52. 52.
    Peng X, Gerzanich V, Anand R, Wang F, Lindstrom J (1997) Chronic Nicotine Treatment Upregulates α3 and α7 Acetylcholine Receptor Subtypes Expressed by the Human Neuroblastoma Cell Line SH-SY5Y. Mol Pharmacol 51(1):776–784PubMedCrossRefGoogle Scholar
  53. 53.
    Serres F, Carney SL (2006) Nicotine regulates SH-SY5Y neuroblastoma cell proliferation through the release of brain-derived neurotrophic factor. Brain Res 1101(1):36–42PubMedCrossRefGoogle Scholar
  54. 54.
    Linert W, Bridge MH, Huber M, Bjugstad KB, Grossman S, Arendash GW (1999) In vitro and in vivo studies investigating possible antioxidant actions of nicotine: Relevance to Parkinson's and Alzheimer's diseases. Biochim Biophys Acta 1454(2):143–152PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departamento de Nutrición y Bioquímica, Facultad de CienciasPontificia Universidad JaverianaBogotáColombia
  2. 2.Departamento de Química, Facultad de CienciasPontificia Universidad JaverianaBogotáColombia
  3. 3.King Fahd Medical Research CenterKing Abdulaziz UniversityJeddahSaudi Arabia
  4. 4.Neurogenic Inflammation Research CenterMashhad University of Medical SciencesMashhadIran
  5. 5.Biotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  6. 6.School of PharmacyMashhad University of Medical SciencesMashhadIran
  7. 7.Facultad de Ciencias de la SaludUniversidad San SebastiánConcepciónChile
  8. 8.Bay Pines VA Healthcare System, Research and Development, Bay Pines VAHCSBay PinesUSA

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