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Neurotoxicity Research

, Volume 35, Issue 3, pp 505–515 | Cite as

Low Molecular Weight Sulfated Chitosan: Neuroprotective Effect on Rotenone-Induced In Vitro Parkinson’s Disease

  • Venkatesan Manigandan
  • Jagatheesan Nataraj
  • Ramachandran Karthik
  • Thamilarasan Manivasagam
  • Ramachandran SaravananEmail author
  • Arokyasamy Justin Thenmozhi
  • Musthafa Mohamed Essa
  • Gilles J. Guillemin
Original Article

Abstract

The present investigation was an attempt to study the effect of low molecular weight sulfated chitosan (LMWSC) on in vitro rotenone model of Parkinson’s disease (PD) by evaluating cell viability, oxidative stress, mitochondrial membrane potential, DNA fragmentation, and apoptosis. Incubation of SH-SY5Y cells with 100 nm rotenone resulted in neuronal cell death, redox imbalanced mitochondrial dysfunction, DNA fragmentation, condensation, and apoptotic cellular morphology. Rotenone exposure enhanced the expression of preapoptotic (cytochrome C (cyto c), caspase-3, -8, -9, and Bax) and down-regulated the expression of anti-apoptotic (Bcl-2) markers. Reduction of the intracellular reactive oxygen species (ROS) levels ensued due to pretreatment of LMWSC along with consequent normalization of antioxidant enzymes, mitigation of rotenone induced mitochondrial dysfunction and apoptosis. Our current findings suggested that LMWSC exhibit the pronounced neuroprotective effects, which could be due to its antioxidant, mitochondrial protection, and anti-apoptotic properties. We thus conclude that LMWSC could be developed as a novel therapeutic molecule for the benefit of reducing the consequences of PD. However, further extensive preclinical and clinical studies are warranted.

Keywords

Sulfated chitosan Rotenone Mitochondrial dysfunction Oxidative stress Apoptosis Neuronal damage 

Notes

Funding Information

The Senior Research Fellowship was funded and supported by the Council of Scientific & Industrial Research (CSIR), New Delhi, India.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing conflict of interest.

Supplementary material

12640_2018_9978_MOESM1_ESM.doc (54 kb)
ESM 1 (DOC 54 kb)

References

  1. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefGoogle Scholar
  2. Alonso D, Castro A, Martinez A (2005) Marine compounds for the therapeutic treatment of neurological disorders. Expert Opin Ther Pat 15:1377–1386CrossRefGoogle Scholar
  3. Ben Mansour R, Ksouri WM, Cluzet S, Krisa S, Richard T, Ksouri R (2016) Assessment of antioxidant activity and neuroprotective capacity on PC12 cell line of Frankenia thymifolia and related phenolic LC-MS/MS identification. Evid Based Complement Alternat Med 2843463:1–8Google Scholar
  4. Borner C (2003) The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol 39:615–647CrossRefGoogle Scholar
  5. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X (1999) Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15:269–290CrossRefGoogle Scholar
  6. Desagher S, Martinou J (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol 10:369–377CrossRefGoogle Scholar
  7. Desai U (2004) New antithrombin-based anticoagulants. Med Res Rev 24:151–181CrossRefGoogle Scholar
  8. Dhanalakshmi C, Manivasagam T, Nataraj J, Justin Thenmozhi A, Essa MM (2015) Neurosupportive role of vanillin, a natural phenolic compound, on rotenone induced neurotoxicity in SH-SY5Y neuroblastoma cells. Evid Based Complement Alternat Med 2015:1–11CrossRefGoogle Scholar
  9. Ding K, Wang Y, Wang H, Yuan L, Tan M, Shi X, Chen H (2014) 6-O-Sulfated chitosan promoting the neural differentiation of mouse embryonic stem cells. ACS Appl Mater Interfaces 6(22):20043–20050CrossRefGoogle Scholar
  10. Drozd N, Sher A, Makarov V, Galbraikh L, Vikhoreva G, Gorbachiova I (2001) Comparison of antithrombin activity of the polysulphate chitosan derivatives in in vivo and in vitro system. Thromb Res 102:445–455CrossRefGoogle Scholar
  11. Ellman G (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 8:70–77CrossRefGoogle Scholar
  12. Ganguly G, Chakrabarti S, Chatterjee U, Saso L (2017) Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer’s disease and Parkinson’s disease. Drug Des Devel Ther 11:797–810CrossRefGoogle Scholar
  13. Gao Y, Dong C, Yin J, Shen J, Tian J, Li C (2012) Neuroprotective effect of fucoidan on H2O2-induced apoptosis in PC12 cells via activation of PI3K/Akt pathway. Cell Mol Neurobiol 32:523–529CrossRefGoogle Scholar
  14. Gilgun-Sherki Y, Melamed E, Offen D (2001) Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 40:959–975CrossRefGoogle Scholar
  15. Guo S, Cui X, Rausch W (2016) Ganoderma Lucidum polysaccharides protect against MPP+ and rotenone-induced apoptosis in primary dopaminergic cell cultures through inhibiting oxidative stress. Am J Neurodegener 5:131Google Scholar
  16. Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255CrossRefGoogle Scholar
  17. Hou X, Si J, Ren H, Chen D, Wang H, Ying Z, Wang (2015) Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells. Acta Pharmacol Sin 36:1300–1307CrossRefGoogle Scholar
  18. Hu L, Lu M, Wu Z, Wong PH, Bian J (2009) Hydrogen sulfide inhibits rotenone-induced apoptosis via preservation of mitochondrial function. Mol Pharmacol 75:27–34CrossRefGoogle Scholar
  19. Hui B, Li J, Geng M (2008) Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, decreased vulnerability of PC12 cells to human immunodeficiency virus tat protein through attenuating calcium overload. J Neurosci Res 86:1169–1177CrossRefGoogle Scholar
  20. Jayaraj R, Tamilselvam K, Manivasagam T, Elangovan N (2013) Neuroprotective effect of CNB-001, a novel pyrazole derivative of curcumin on biochemical and apoptotic markers against rotenone-induced SK-N-SH cellular model of Parkinson’s disease. J Mol Neurosci 51:863–870CrossRefGoogle Scholar
  21. Jin H, Kanthasamy A, Ghosh A, Anantharam V, Kalyanaraman B, Kanthasamy A (2014) Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes. Biochim Biophys Acta Mol basis Dis 1842:1282–1294CrossRefGoogle Scholar
  22. Johnson M, Bobrovskaya L (2015) An update on the rotenone models of Parkinson's disease: their ability to reproduce the features of clinical disease and model gene–environment interaction. Neurotoxicology 46:101–116CrossRefGoogle Scholar
  23. Kakkar P, Das B, Viswanathan P (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132Google Scholar
  24. Kalia L, Lang A (2015) Parkinson disease. Lan 386:896–912CrossRefGoogle Scholar
  25. Kalia L, Lang A (2016) Parkinson disease in 2015: evolving basic, pathological and clinical concepts in PD. Nat Rev Neurol 12:65–66CrossRefGoogle Scholar
  26. Karthik R, Manigandan V, Saravanan R, Rajesh R, Chandrika B (2016) Structural characterization and in vitro biomedical activities of sulfated chitosan from Sepia pharaonis. Int J Biol Macromol 84:319–328CrossRefGoogle Scholar
  27. Koppula S, Kumar H, More S, Kim B, Kim I, Choi D (2012) Recent advances on the neuroprotective potential of antioxidants in experimental models of Parkinson’s disease. Int J Mol Sci 13:10608–10629CrossRefGoogle Scholar
  28. Koudelova J, Mourek J (1994) The lipid peroxidation in various parts of the rat brain: effect of age hypoxia and hyperoxia. Physiol Res 43:169–173Google Scholar
  29. Li S, Dai S, Shah NP (2017) Sulfonation and antioxidative evaluation of polysaccharides from Pleurotus mushroom and Streptococcus thermophilus bacteria: a review. Compr Rev Food Sci Food Saf 16(2):282–294Google Scholar
  30. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and developmental settings. Adv Drug Deliv Rev 23:3–25CrossRefGoogle Scholar
  31. Liu S, Zhou J, Zhang X, Liu Y, Chen J, Hu B, Zhang Y (2016) Strategies to optimize adult stem cell therapy for tissue regeneration. Int J Mol Sci 17(6):982CrossRefGoogle Scholar
  32. Luan F, Wei L, Zhang J, Mi Y, Dong F, Li Q, Guo Z (2018) Antioxidant activity and antifungal activity of chitosan derivatives with propane sulfonate groups. Polymer 10(4):395CrossRefGoogle Scholar
  33. Miller GM, Hsieh-Wilson LC (2015) Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans. Exp Neurol 274:115–125CrossRefGoogle Scholar
  34. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Met 65:55–63CrossRefGoogle Scholar
  35. Narang S, Gibson D, Wasan A, Ross E, Michna E, Nedeljkovic S, Jamison R (2008) Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J Pain 9:254–264CrossRefGoogle Scholar
  36. Nataraj J, Manivasagam T, Justin Thenmozhi A, Essa MM (2017) Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells. Nutr Neurosci 20:351–359CrossRefGoogle Scholar
  37. Ngo DH, Kim SK (2013) Sulfated polysaccharides as bioactive agents from marine algae. Int J Biol Macromol 62:70–75CrossRefGoogle Scholar
  38. Pangestuti R, Kim S (2010) Neuroprotective properties of chitosan and its derivatives. Mar Drugs 8:2117–2128CrossRefGoogle Scholar
  39. Persin Z, Stana-Kleinschek K, Foster TJ, Van Dam JE, Boeriu CG, Navard P (2011) Challenges and opportunities in polysaccharides research and technology: the EPNOE views for the next decade in the areas of materials, food and health care. Carbohydr Polym 84(1):22–32CrossRefGoogle Scholar
  40. Poewe W, Seppi K, Tanner C, Halliday G, Brundin P, Volkmann J, Lang A (2017) Parkinson disease. Nat Rev Dis Primers 3:17013CrossRefGoogle Scholar
  41. Rotruck J, Pope A, Ganther H, Swanson A, Hafeman D, Hoekstra W (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590CrossRefGoogle Scholar
  42. Sanders L, Greenamyre J (2013) Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radic Biol Med 62:111–120CrossRefGoogle Scholar
  43. Shao P, Chen M, Pei Y, Sun P (2013) In intro antioxidant activities of different sulfated polysaccharides from chlorophytan seaweeds Ulva fasciata. Int J Biol Macromol 59:295–300CrossRefGoogle Scholar
  44. Shulman J, De Jager P, Feany M (2011) Parkinson’s disease: genetics and pathogenesis. Annu Rev Pathol Mech 6:193–222CrossRefGoogle Scholar
  45. Si X, Zhou Z, Bu D, Li J, Strappe P, Blanchard C (2016) Effect of sulfation on the antioxidant properties and in vitro cell proliferation characteristics of polysaccharides isolated from corn bran. CyTA-J Food 14(4):555–564Google Scholar
  46. Soares da Costa D, Reis RL, Pashkuleva I (2017) Sulfation of glycosaminoglycans and its implications in human health and disorders. Annu Rev Biomed Eng 19:1–26CrossRefGoogle Scholar
  47. Subhapradha N, Suman S, Ramasamy P, Saravanan R, Shanmugam V, Srinivasan A, Shanmugam A (2013) Anticoagulant and antioxidant activity of sulfated chitosan from the shell of donacid clam Donax scortum (Linnaeus, 1758). Int J Nutr Pharmacol Neurol Dis 3:39–45CrossRefGoogle Scholar
  48. Tamilselvam K, Braidy N, Manivasagam T, Essa MM, Prasad NR, Karthikeyan S, Guillemin G (2013) Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson’s disease. Oxidative Med Cell Longev 2013:1–12CrossRefGoogle Scholar
  49. Testa C, Sherer T, Greenamyre J (2005) Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Mol Brain Res 134:109–118CrossRefGoogle Scholar
  50. Tufekci K, Civi Bayin E, Genc S, Genc K (2011) The Nrf2/ARE pathway: a promising target to counteract mitochondrial dysfunction in Parkinson’s disease. Parkinson’s Dis 314082:1–14Google Scholar
  51. Wang J, Liu H, Jin W, Zhang H, Zhang Q (2016a) Structure–activity relationship of sulfated hetero/galactofucan polysaccharides on dopaminergic neuron. Int J Biol Macromol 82:878–883CrossRefGoogle Scholar
  52. Wang T, Zhu M, He ZZ (2016b) Low-molecular-weight fucoidan attenuates mitochondrial dysfunction and improves neurological outcome after traumatic brain injury in aged mice: involvement of Sirt3. Cell Mol Neurobiol 36(8):1257–1268CrossRefGoogle Scholar
  53. Wang J, Liu H, Zhang X, Li X, Geng L, Zhang H, Zhang Q (2017) Sulfated hetero-polysaccharides protect SH-SY5Y cells from H2O2-induced apoptosis by affecting the PI3K/Akt signaling pathway. Mar Drugs 15:110CrossRefGoogle Scholar
  54. Watabe M, Nakaki T (2004) Rotenone induces apoptosis via activation of bad in human dopaminergic SH-SY5Y cells. J Pharmacol Exp Ther 311:948–953CrossRefGoogle Scholar
  55. Wu Q, Zheng C, Ning ZX, Yang B (2007) Modification of low molecular weight polysaccharides from Tremella fuciformis and their antioxidant activity in vitro. Int J Mol Sci 8(7):670–679CrossRefGoogle Scholar
  56. Xie Z, Ding S, Shen Y (2014) Silibinin activates AMP-activated protein kinase to protect neuronal cells from oxygen and glucose deprivation-re-oxygenation. Biochem Biophys Res Commun 454:313–319CrossRefGoogle Scholar
  57. Yan JK, Wang WQ, Ma HL, Wu JY (2012) Sulfation and enhanced antioxidant capacity of an exopolysaccharide produced by the medicinal fungus Cordyceps sinensis. Molecules 18(1):167–177CrossRefGoogle Scholar
  58. Youdim M, Weinreb O, Mandel S, Amit T (2009) Neuroprotective molecular mechanisms of (−)-epigallocatechin-3-gallate: a reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes Nutr 4:283CrossRefGoogle Scholar
  59. Zhang G, Li P, Li Y, Liu X, Chen Y, Weng X, Zhu X (2011) Fucoidan by inhibiting cathepsin D activities alleviates PC12 apoptosis induced by hydrogen peroxide. J Chin Mater Med 36:1083–1086Google Scholar
  60. Zhang L, Hao J, Zheng Y, Su R, Liao Y, Gong X, Liu L, Wang X (2018) Fucoidan protects dopaminergic neurons by enhancing the mitochondrial function in a rotenone-induced rat model of Parkinson’s disease. Aging Dis 9(4):590–604CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Venkatesan Manigandan
    • 1
  • Jagatheesan Nataraj
    • 2
  • Ramachandran Karthik
    • 1
  • Thamilarasan Manivasagam
    • 2
  • Ramachandran Saravanan
    • 1
    Email author
  • Arokyasamy Justin Thenmozhi
    • 2
  • Musthafa Mohamed Essa
    • 3
    • 4
  • Gilles J. Guillemin
    • 5
  1. 1.Native Medicine and Marine Pharmacology Laboratory, Department of Medical Biotechnology, Faculty of Allied Health SciencesChettinad Academy of Research and EducationChennaiIndia
  2. 2.Department of Biochemistry and BiotechnologyAnnamalai UniversityAnnamalai NagarIndia
  3. 3.Department of Food Science and Nutrition, CAMSSultan Qaboos UniversityMuscatOman
  4. 4.Ageing and Dementia Research GroupSultan Qaboos UniversityMuscatOman
  5. 5.Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, Australian School of Advanced MedicineMacquarie UniversitySydneyAustralia

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