Advertisement

Protection of Oxidant-Induced Neuronal Cells Injury by a Unique Cruciferous Nutraceutical

  • Zhenquan Jia
  • Soumya Saha
  • Hong Zhu
  • Yunbo Li
  • Hara P. MisraEmail author
Chapter
  • 1.1k Downloads
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

The involvement of reactive oxygen species and electrophiles in the pathogenesis of various neurodegenerative disorders has stimulated extensive studies on the use of exogenous antioxidative compounds to prevent oxidative neurodegenerative processes with few effects. In this study, we demonstrated that the cruciferous nutraceutical 3H-1,2-dithiole-3-thione (D3T) at micromolar concentrations (10–100 μM) has the potential to induce the levels of reduced glutathione (GSH) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two crucial cellular defenses against oxidative and electrophilic stress in human neuroblastoma cells (SH-SY5Y), human primary neurons and astrocytes. In addition, pretreatment with D3T protected cells from oxidative and electrophilic neurocytotoxicity induced by various neurotoxicants, including acrolein, 4-hydroxy-2-nonenal (HNE), 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+). The results of this study may have important implications for the development of novel neuroprotective strategies against neurodegenerative disorders underlying Parkinson’s disease.

Keywords

Astrocytes Neuronal cells Neurotoxicity ROS 

Abbreviations

6-OHDA

6-Hydroxydopamine

BSA

Bovine serum albumin

D3T

3H-1,2-Dithiole-3-thione

DCIP

2,6-Dichloroindophenol

GPx

Glutathione peroxidase

GSH

Reduced glutathione

GST

Glutathione S-transferase

HNE

4-Hydroxy-2-nonenal

MPP+

1-Methyl-4-phenylpyridinium

MTT

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium

NQO1

NAD(P)H:quinone oxidoreductase 1

ROS

Reactive oxygen species

SOD

Superoxide dismutase

References

  1. 1.
    Ischiropoulos, H., Beckman, J. S. (2003) Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest 111, 163–9.PubMedGoogle Scholar
  2. 2.
    LoPachin, R. M., Barber, D. S., Gavin, T. (2008) Molecular mechanisms of the conjugated alpha, beta-unsaturated carbonyl derivatives: relevance to neurotoxicity and neurodegenerative diseases Toxicol Sci 104, 235–49.Google Scholar
  3. 3.
    Metodiewa, D., Koska, C. (2000) Reactive oxygen species and reactive nitrogen species: relevance to cyto(neuro)toxic events and neurologic disorders. An overview Neurotox Res 1, 197–233.CrossRefGoogle Scholar
  4. 4.
    Alam, Z. I., Daniel, S. E., Lees, A. J., Marsden, D. C., Jenner, P., Halliwell, B. (1997) A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease J Neurochem 69, 1326–9.PubMedGoogle Scholar
  5. 5.
    Alam, Z. I., Jenner, A., Daniel, S. E., et al. (1997) Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra J Neurochem 69, 1196–203.Google Scholar
  6. 6.
    Selley, M. L. (1998) (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease Free Radic Biol Med 25, 169–74.Google Scholar
  7. 7.
    Storey, K. B. (1996) Oxidative stress: animal adaptations in nature Braz J Med Biol Res 29, 1715–33.Google Scholar
  8. 8.
    Ross, D., Kepa, J. K., Winski, S. L., Beall, H. D., Anwar, A., Siegel, D. (2000) NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms Chem Biol Interact 129, 77–97.Google Scholar
  9. 9.
    Spencer, J. P., Jenner, P., Daniel, S. E., Lees, A. J., Marsden, D. C., Halliwell, B. (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease: possible mechanisms of formation involving reactive oxygen species J Neurochem 71, 2112–22.Google Scholar
  10. 10.
    Sofic, E., Lange, K. W., Jellinger, K., Riederer, P. (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease Neurosci Lett 142, 128–30.Google Scholar
  11. 11.
    Sechi, G., Deledda, M. G., Bua, G., et al. (1996) Reduced intravenous glutathione in the treatment of early Parkinson’s disease Prog Neuropsychopharmacol Biol Psychiatry 20, 1159–70.CrossRefGoogle Scholar
  12. 12.
    Spencer, J. P., Jenner, P., Halliwell, B. (1995) Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine. Relevance to Parkinson’s disease Neuroreport 6, 1480–4.Google Scholar
  13. 13.
    Perry, T. L., Godin, D. V., Hansen, S. (1982) Parkinson’s disease: a disorder due to nigral glutathione deficiency? Neurosci Lett 33, 305–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Perry, T. L., Yong, V. W. (1986) Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients Neurosci Lett 67, 269–74.Google Scholar
  15. 15.
    Lai, C. T., Yu, P. H. (1997) Dopamine- and L-beta-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Effects of oxidative stress and antioxidative factors Biochem Pharmacol 53, 363–72.Google Scholar
  16. 16.
    Pong, K., Doctrow, S. R., Baudry, M. (2000) Prevention of 1-methyl-4-phenylpyridinium- and 6-hydroxydopamine-induced nitration of tyrosine hydroxylase and neurotoxicity by EUK-134, a superoxide dismutase and catalase mimetic, in cultured dopaminergic neurons Brain Res 881, 182–9.Google Scholar
  17. 17.
    Mazzio, E., Huber, J., Darling, S., Harris, N., Soliman, K. F. (2001) Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells Neurotoxicology 22, 283–8.Google Scholar
  18. 18.
    Stull, N. D., Polan, D. P., Iacovitti, L. (2002) Antioxidant compounds protect dopamine neurons from death due to oxidative stress in vitro Brain Res 931, 181–5.Google Scholar
  19. 19.
    Halliwell, B. (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment Drugs Aging 18, 685–716.Google Scholar
  20. 20.
    Martinovits, G., Melamed, E., Cohen, O., Rosenthal, J., Uzzan, A. (1986) Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) Neurosci Lett 69, 192–7.Google Scholar
  21. 21.
    Perry, T. L., Yong, V. W., Hansen, S., et al. (1987) Alpha-tocopherol and beta-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine J Neurol Sci 81, 321–31.Google Scholar
  22. 22.
    Shoulson, I. (1998) DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism Ann Neurol 44, S160–6.Google Scholar
  23. 23.
    Ebadi, M., Srinivasan, S. K., Baxi, M. D. (1996) Oxidative stress and antioxidant therapy in Parkinson’s disease Prog Neurobiol 48, 1–19.Google Scholar
  24. 24.
    Ratnam, D. V., Ankola, D. D., Bhardwaj, V., Sahana, D. K., Kumar, M. N. (2006) Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective J Control Release 113, 189–207.Google Scholar
  25. 25.
    Zhu, H., Cao, Z., Zhang, L., Trush, M. A., Li, Y. (2007) Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle cells: chemical inducibility and protection against reactive oxygen and nitrogen species-induced injury Mol Cell Biochem 301, 47–59.Google Scholar
  26. 26.
    Zhu, H., Zhang, L., Trush, M. A., Li, Y. (2007) Upregulation of endogenous glutathione ­system by 3 H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury Free Radic Res 41, 242–50.Google Scholar
  27. 27.
    Kwak, M. K., Egner, P. A., Dolan, P. M., et al. (2001) Role of phase 2 enzyme induction in chemoprotection by dithiolethiones Mutat Res 480–481, 305–15.Google Scholar
  28. 28.
    Cao, Z., Hardej, D., Trombetta, L. D., Trush, M. A., Li, Y. (2003) Induction of cellular glutathione and glutathione S-transferase by 3 H-1,2-dithiole-3-thione in rat aortic smooth muscle A10 cells: protection against acrolein-induced toxicity Atherosclerosis 166, 291–301.Google Scholar
  29. 29.
    Peng, X., Li, Y. (2002) Induction of cellular glutathione-linked enzymes and catalase by the unique chemoprotective agent, 3 H-1,2-dithiole-3-thione in rat cardiomyocytes affords protection against oxidative cell injury Pharmacol Res 45, 491–7.Google Scholar
  30. 30.
    Hissin, P. J., Hilf, R. (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues Anal Biochem 74, 214–26.Google Scholar
  31. 31.
    Benson, A. M., Hunkeler, M. J., Talalay, P. (1980) Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity Proc Natl Acad Sci USA 77, 5216–20.Google Scholar
  32. 32.
    Jia, Z., Hallur, S., Zhu, H., Li, Y., Misra, H. P. (2008) Potent upregulation of glutathione and NAD(P)H:quinone oxidoreductase 1 by alpha-lipoic acid in human neuroblastoma SH-SY5Y cells: protection against neurotoxicant-elicited cytotoxicity Neurochem Res 33, 790–800.Google Scholar
  33. 33.
    Jia, Z., Zhu, H., Misra, B. R., Li, Y., Misra, H. P. (2008) Dopamine as a potent inducer of cellular glutathione and NAD(P)H:quinone oxidoreductase 1 in PC12 neuronal cells: a potential adaptive mechanism for dopaminergic neuroprotection Neurochem Res 33, 2197–205.Google Scholar
  34. 34.
    Kehrer, J. P. (1993) Free radicals as mediators of tissue injury and disease Crit Rev Toxicol 23, 21–48.CrossRefGoogle Scholar
  35. 35.
    Pahlman, S., Ruusala, A. I., Abrahamsson, L., Mattsson, M. E., Esscher, T. (1984) Retinoic acid-induced differentiation of cultured human neuroblastoma cells: a comparison with phorbolester-induced differentiation Cell Differ 14, 135–44.Google Scholar
  36. 36.
    Siegel, D., Bolton, E. M., Burr, J. A., Liebler, D. C., Ross, D. (1997) The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant Mol Pharmacol 52, 300–5.Google Scholar
  37. 37.
    Siegel, D., Gustafson, D. L., Dehn, D. L., et al. (2004) NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger Mol Pharmacol 65, 1238–47.Google Scholar
  38. 38.
    Ross, D. (2004) Quinone reductases multitasking in the metabolic world Drug Metab Rev 36, 639–54.CrossRefGoogle Scholar
  39. 39.
    Zafar, K. S., Inayat-Hussain, S. H., Siegel, D., Bao, A., Shieh, B., Ross, D. (2006) Overexpression of NQO1 protects human SK-N-MC neuroblastoma cells against dopamine-induced cell death Toxicol Lett 166, 261–7.Google Scholar
  40. 40.
    Berman, S. B., Hastings, T. G. (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease J Neurochem 73, 1127–37.Google Scholar
  41. 41.
    Kimelberg, H. K., Norenberg, M. D. (1989) Astrocytes Sci Am 260, 66–72, 4, 6.Google Scholar
  42. 42.
    de Lau, L. M. L., Bornebroek, M., Witteman, J. C. M., Hofman, A., Koudstaal, P. J., Breteler, M. M. B. (2005) Dietary fatty acids and the risk of Parkinson disease The Rotterdam Study Neurology 64, 2040–5.Google Scholar
  43. 43.
    Heo, H. J., Lee, C. Y. (2006) Phenolic phytochemicals in cabbage inhibit amyloid ?protein-induced neurotoxicity LWT-Food Science and Technology 39, 331–7.Google Scholar
  44. 44.
    Mattson, M. P., Son, T. G., Camandola, S. (2007) Viewpoint: mechanisms of action and therapeutic potential of neurohormetic phytochemicals Dose Response 5, 174–86.Google Scholar
  45. 45.
    Joshipura, K. J., Ascherio, A., Manson, J. E., et al. (1999) Fruit and vegetable intake in relation to risk of ischemic stroke Jama 282, 1233–9.Google Scholar
  46. 46.
    Ullah, M. F., Khan, M. W. (2008) Food as medicine: potential therapeutic tendencies of plant derived polyphenolic compounds Asian Pac J Cancer Prev 9, 187–95.Google Scholar
  47. 47.
    Zhu, H., Itoh, K., Yamamoto, M., Zweier, J. L., Li, Y. (2005) Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury FEBS Lett 579, 3029–36.Google Scholar
  48. 48.
    Zhu, H., Zhang, L., Itoh, K., et al. (2006) Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress Free Radic Biol Med 41, 132–43.Google Scholar
  49. 49.
    Kobayashi, M., Yamamoto, M. (2006) Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species Adv Enzyme Regul 46, 113–40.Google Scholar
  50. 50.
    Yoritaka, A., Hattori, N., Uchida, K., Tanaka, M., Stadtman, E. R., Mizuno, Y. (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease Proc Natl Acad Sci USA 93, 2696–701.Google Scholar
  51. 51.
    Cao, Z., Hardej, D., Trombetta, L. D., Li, Y. (2003) The role of chemically induced glutathione and glutathione S-transferase in protecting against 4-hydroxy-2-nonenal-mediated cytotoxicity in vascular smooth muscle cells Cardiovasc Toxicol 3, 165–77.Google Scholar
  52. 52.
    Cao, Z., Zhu, H., Zhang, L., Zhao, X., Zweier, J. L., Li, Y. (2006) Antioxidants and phase 2 enzymes in cardiomyocytes: Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury Exp Biol Med (Maywood) 231, 1353–64.Google Scholar
  53. 53.
    Jia, Z., Misra, B. R., Zhu, H., Li, Y., Misra, H. P. (2009) Upregulation of cellular glutathione by 3 H-1,2-dithiole-3-thione as a possible treatment strategy for protecting against acrolein-induced neurocytotoxicity Neurotoxicology 30, 1–9.Google Scholar
  54. 54.
    Peuchen, S., Bolanos, J. P., Heales, S. J. R., Almeida, A., Duchen, M. R., Clark, J. B. (1997) Interrelationships between astrocyte function, oxidative stress and antioxidant status within the central nervous system Progress in Neurobiology 52, 261–81.Google Scholar
  55. 55.
    Wilson, J. X. (1997) Antioxidant defense of the brain: a role for astrocytes CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 75, 1149–63.Google Scholar
  56. 56.
    Dringen, R. (2000) Metabolism and functions of glutathione in brain Progress in Neurobiology 62, 649–71.CrossRefGoogle Scholar
  57. 57.
    Chen, Y., Vartiainen, N. E., Ying, W., Chan, P. H., Koistinaho, J., Swanson, R. A. (2001) Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism J Neurochem 77, 1601–10.Google Scholar
  58. 58.
    Smythies, J. (1999) The neurotoxicity of glutamate, dopamine, iron and reactive oxygen species: functional interrelationships in health and disease: a review-discussion Neurotox Res 1, 27–39.Google Scholar
  59. 59.
    Shimizu, E., Hashimoto, K., Komatsu, N., Iyo, M. (2002) Roles of endogenous glutathione levels on 6-hydroxydopamine-induced apoptotic neuronal cell death in human neuroblastoma SK-N-SH cells Neuropharmacology 43, 434–43.Google Scholar
  60. 60.
    Di Monte, D. A., Wu, E. Y., Langston, J. W. (1992) Role of astrocytes in MPTP metabolism and toxicity Ann N Y Acad Sci 648, 219–28.CrossRefGoogle Scholar
  61. 61.
    Adams, J. D., Jr., Klaidman, L. K., Leung, A. C. (1993) MPP+ and MPDP+ induced oxygen radical formation with mitochondrial enzymes Free Radic Biol Med 15, 181–6.Google Scholar
  62. 62.
    Rojas, P., Rios, C. (1993) Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice Pharmacol Toxicol 72, 364–8.Google Scholar
  63. 63.
    Smith, T. S., Bennett, J. P., Jr. (1997) Mitochondrial toxins in models of neurodegenerative diseases. I: In vivo brain hydroxyl radical production during systemic MPTP treatment or following microdialysis infusion of methylpyridinium or azide ions Brain Res 765, 183–8.PubMedGoogle Scholar
  64. 64.
    Zang, L. Y., Misra, H. P. (1993) Generation of reactive oxygen species during the monoamine oxidase-catalyzed oxidation of the neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine J Biol Chem 268, 16504–12.Google Scholar
  65. 65.
    Zang, L. Y., Misra, H. P. (1992) Superoxide radical production during the autoxidation of 1-methyl-4-phenyl-2,3-dihydropyridinium perchlorate J Biol Chem 267, 17547–52.Google Scholar
  66. 66.
    Grant, C. M., Perrone, G., Dawes, I. W. (1998) Glutathione and catalase provide overlapping defenses for protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae Biochem Biophys Res Commun 253, 893–8.Google Scholar
  67. 67.
    Wang, J. S., Shen, X., He, X., et al. (1999) Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People’s Republic of China. J Natl Cancer Inst 91, 347–54.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Zhenquan Jia
  • Soumya Saha
  • Hong Zhu
  • Yunbo Li
  • Hara P. Misra
    • 1
    Email author
  1. 1.Edward Via Virginia College of Osteopathic MedicineBlacksburgUSA

Personalised recommendations