Skip to main content
SpringerLink
Log in

Protective Effect of Lycopene on Oxidative Stress and Cognitive Decline in Rotenone Induced Model of Parkinson’s Disease

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Evidence from clinical and experimental studies indicate that oxidative stress is involved in pathogenesis of Parkinson’s disease. The present study was designed to investigate the neuroprotective potential of lycopene on oxidative stress and neurobehavioral abnormalities in rotenone induced PD. Rats were treated with rotenone (3 mg/kg body weight, intraperitoneally) for 30 days. NADH dehydrogenase a marker of rotenone action was observed to be significantly inhibited (35%) in striatum of treated animals. However, lycopene administration (10 mg/kg, orally) to the rotenone treated animals for 30 days increased the activity by 39% when compared to rotenone treated animals. Rotenone administration increased the MDA levels (75.15%) in striatum, whereas, lycopene administration to rotenone treated animals decreased the levels by 24.33%. Along with this, significant decrease in GSH levels (42.69%) was observed in rotenone treated animals. Lycopene supplementation on the other hand, increased the levels of GSH by 75.35% when compared with rotenone treated group. The activity of SOD was inhibited by 69% in rotenone treated animals and on lycopene supplementation; the activity increased by 12% when compared to controls. This was accompanied by cognitive and motor deficits in rotenone administered animals, which were reversed on lycopene treatment. Lycopene treatment also prevented release of cytochrome c from mitochondria. Collectively, these observations suggest that lycopene supplementation along with rotenone for 30 days prevented rotenone-induced alterations in antioxidants along with the prevention of rotenone induced oxidative stress and neurobehavioral deficits. The results provide an evidence for beneficial effect of lycopene supplementation in rotenone-induced PD and suggest therapeutic potential in neurodegenerative diseases involving accentuated oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

PD:

Parkinson’s disease

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

GSH:

Glutathione

AChE:

Acetylcholinesterase

GPx:

Glutathione peroxidase

PMS:

Post mitochondrial supernatant

CAT:

Catalase

H2O2 :

Hydrogen peroxide

DTNB:

5,5′ Dithio-bis-2-nitrobenzoate

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

AD:

Alzheimer’s disease

References

  1. Hald A, Lotharius J (2005) Oxidative stress and inflammation in Parkinson’s disease: is there a causal link? Exp Neurol 193:279–290

    Article  PubMed  CAS  Google Scholar 

  2. Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R (2007) How common are the “common” neurologic disorders? Neurology 68:326–337

    Article  PubMed  CAS  Google Scholar 

  3. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376

    Article  PubMed  CAS  Google Scholar 

  4. Maj MC, Tkachyova I, Patel P, Addis JB, Mackay N, Levandovskiy V, Lee J, Lang AE, Cameron JM, Robinson BH (2010) Oxidative stress alters the regulatory control of p66Shc and Akt in PINK1 deficient cells. Biochem Biophys Res Commun 399:331–335

    Article  PubMed  CAS  Google Scholar 

  5. Stocchi F, Olanow CW (2003) Neuroprotection in Parkinson’s disease: clinical trials. Ann Neurol 53(Suppl 3):S87–97 discussion S97-89

    Article  PubMed  CAS  Google Scholar 

  6. Beal MF (2001) Experimental models of Parkinson’s disease. Nat Rev Neurosci 2:325–334

    Article  PubMed  CAS  Google Scholar 

  7. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    Article  PubMed  CAS  Google Scholar 

  8. Alam M, Schmidt WJ (2002) Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 136:317–324

    Article  PubMed  CAS  Google Scholar 

  9. 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 3:1301–1306

    Article  PubMed  CAS  Google Scholar 

  10. Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT (2003) Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci 23:10756–10764

    PubMed  CAS  Google Scholar 

  11. Chen L, Ding Y, Cagniard B, Van Laar AD, Mortimer A, Chi W, Hastings TG, Kang UJ, Zhuang X (2008) Unregulated cytosolic dopamine causes neurodegeneration associated with oxidative stress in mice. J Neurosci 28:425–433

    Article  PubMed  Google Scholar 

  12. Weinreb O, Amit T, Mandel S, Youdim MB (2009) Neuroprotective molecular mechanisms of (−)-epigallocatechin-3-gallate: a reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes Nutr 4:283–296

    Article  CAS  Google Scholar 

  13. Wang MS, Boddapati S, Emadi S, Sierks MR (2010) Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson’s disease cell model. BMC Neurosci 11:57

    Article  PubMed  Google Scholar 

  14. Lu KT, Ko MC, Chen BY, Huang JC, Hsieh CW, Lee MC, Chiou RY, Wung BS, Peng CH, Yang YL (2008) Neuroprotective effects of resveratrol on MPTP-induced neuron loss mediated by free radical scavenging. J Agric Food Chem 56:6910–6913

    Article  PubMed  CAS  Google Scholar 

  15. Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K (2008) Antioxidants in central nervous system diseases: preclinical promise and translational challenges. J Alzheimers Dis 15:473–493

    PubMed  CAS  Google Scholar 

  16. Conn PF, Schalch W, Truscott TG (1991) The singlet oxygen and carotenoid interaction. J Photochem Photobiol B 11:41–47

    Article  PubMed  CAS  Google Scholar 

  17. Miller NJ, Sampson J, Candeias LP, Bramley PM, Rice-Evans CA (1996) Antioxidant activities of carotenes and xanthophylls. FEBS Lett 384:240–242

    Article  PubMed  CAS  Google Scholar 

  18. Mortensen A, Skibsted LH, Sampson J, Rice-Evans C, Everett SA (1997) Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett 418:91–97

    Article  PubMed  CAS  Google Scholar 

  19. Muzandu K, Ishizuka M, Sakamoto KQ, Shaban Z, El Bohi K, Kazusaka A, Fujita S (2006) Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications. Toxicol Appl Pharmacol 215:330–340

    Article  PubMed  CAS  Google Scholar 

  20. Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP (2007) Lycopene as a natural protector against gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes in vitro. Biochim Biophys Acta 1770:659–665

    PubMed  CAS  Google Scholar 

  21. Sengupta A, Das S (1999) The anti-carcinogenic role of lycopene, abundantly present in tomato. Eur J Cancer Prev 8:325–330

    Article  PubMed  CAS  Google Scholar 

  22. Gerster H (1997) The potential role of lycopene for human health. J Am Coll Nutr 16:109–126

    PubMed  CAS  Google Scholar 

  23. Shukla SK, Gupta S, Ojha SK, Sharma SB (2010) Cardiovascular friendly natural products: a promising approach in the management of CVD. Nat Prod Res 24:873–898

    Article  PubMed  CAS  Google Scholar 

  24. Sesso HD, Buring JE, Norkus EP, Gaziano JM (2004) Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women. Am J Clin Nutr 79:47–53

    PubMed  CAS  Google Scholar 

  25. Wei Y, Shen X, Shen H, Mai J, Wu M, Yao G (2010) Effects of lycopene on cerebral ischemia-reperfusion injury in rats. Wei Sheng Yan Jiu 39:201–204

    PubMed  CAS  Google Scholar 

  26. Hsiao G, Fong TH, Tzu NH, Lin KH, Chou DS, Sheu JR (2004) A potent antioxidant, lycopene, affords neuroprotection against microglia activation and focal cerebral ischemia in rats. In Vivo 18:351–356

    PubMed  CAS  Google Scholar 

  27. Sandhir R, Mehrotra A, Kamboj SS (2010) Lycopene prevents 3-nitropropionic acid-induced mitochondrial oxidative stress and dysfunctions in nervous system. Neurochem Int 57:579–587

    Article  PubMed  CAS  Google Scholar 

  28. Kumar P, Kalonia H, Kumar A (2009) Lycopene modulates nitric oxide pathways against 3-nitropropionic acid-induced neurotoxicity. Life Sci 85:711–718

    Article  PubMed  CAS  Google Scholar 

  29. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  30. Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Whittaker M (1984) Cholinesterases. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 52–74

    Google Scholar 

  33. Perez-Pinzon MA, Xu GP, Born J, Lorenzo J, Busto R, Rosenthal M, Sick TJ (1999) Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia. J Cereb Blood Flow Metab 19:39–43

    Article  PubMed  CAS  Google Scholar 

  34. Itoh J, Nabeshima T, Kameyama T (1991) Utility of an elevated plus-maze for dissociation of amnesic and behavioral effects of drugs in mice. Eur J Pharmacol 194:71–76

    Article  PubMed  CAS  Google Scholar 

  35. Allbutt HN, Henderson JM (2007) Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson’s disease. J Neurosci Methods 159:195–202

    Article  PubMed  Google Scholar 

  36. Beal MF (1998) Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta 1366:211–223

    Article  PubMed  CAS  Google Scholar 

  37. Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M, Aksenova M, Gabbita SP, Wu JF, Carney JM et al (1995) Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J Neurochem 65:2146–2156

    Article  PubMed  CAS  Google Scholar 

  38. Adams JD Jr, Chang ML, Klaidman L (2001) Parkinson’s disease—redox mechanisms. Curr Med Chem 8:809–814

    PubMed  CAS  Google Scholar 

  39. Navarro A, Boveris A (2009) Brain mitochondrial dysfunction and oxidative damage in Parkinson’s disease. J Bioenerg Biomembr 41:517–521

    Article  PubMed  CAS  Google Scholar 

  40. Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT (2002) An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22:7006–7015

    PubMed  CAS  Google Scholar 

  41. Koutsilieri E, Scheller C, Grunblatt E, Nara K, Li J, Riederer P (2002) Free radicals in Parkinson’s disease. J Neurol 249(Suppl 2):ll1–ll5

    Google Scholar 

  42. Adams JD Jr, Odunze IN (1991) Oxygen free radicals and Parkinson’s disease. Free Radic Biol Med 10:161–169

    Article  PubMed  CAS  Google Scholar 

  43. Singh C, Ahmad I, Kumar A (2007) Pesticides and metals induced Parkinson’s disease: involvement of free radicals and oxidative stress. Cell Mol Biol (Noisy-le-grand) 53:19–28

    CAS  Google Scholar 

  44. Wertz K, Siler U, Goralczyk R (2004) Lycopene: modes of action to promote prostate health. Arch Biochem Biophys 430:127–134

    Article  PubMed  CAS  Google Scholar 

  45. Matos HR, Di Mascio P, Medeiros MH (2000) Protective effect of lycopene on lipid peroxidation and oxidative DNA damage in cell culture. Arch Biochem Biophys 383:56–59

    Article  PubMed  CAS  Google Scholar 

  46. Kweon GR, Marks JD, Krencik R, Leung EH, Schumacker PT, Hyland K, Kang UJ (2004) Distinct mechanisms of neurodegeneration induced by chronic complex I inhibition in dopaminergic and non-dopaminergic cells. J Biol Chem 279:51783–51792

    Article  PubMed  CAS  Google Scholar 

  47. Cai J, Yang J, Jones DP (1998) Mitochondrial control of apoptosis: the role of cytochrome c. Biochim Biophys Acta 1366:139–149

    Article  PubMed  CAS  Google Scholar 

  48. Marella M, Seo BB, Yagi T, Matsuno-Yagi A (2009) Parkinson’s disease and mitochondrial complex I: a perspective on the Ndi1 therapy. J Bioenerg Biomembr 41:493–497

    Article  PubMed  CAS  Google Scholar 

  49. Jain A, Martensson J, Stole E, Auld PA, Meister A (1991) Glutathione deficiency leads to mitochondrial damage in brain. Proc Natl Acad Sci USA 88:1913–1917

    Article  PubMed  CAS  Google Scholar 

  50. Pearce RK, Owen A, Daniel S, Jenner P, Marsden CD (1997) Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease. J Neural Transm 104:661–677

    Article  PubMed  CAS  Google Scholar 

  51. Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52:381–389

    Article  PubMed  CAS  Google Scholar 

  52. Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355

    Article  PubMed  CAS  Google Scholar 

  53. Alam ZI, Daniel SE, Lees AJ, Marsden DC, 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 69:1326–1329

    Article  PubMed  CAS  Google Scholar 

  54. Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004) Characterization of superoxide-producing sites in isolated brain mitochondria. J Biol Chem 279:4127–4135

    Article  PubMed  CAS  Google Scholar 

  55. Wei H, Meng Z (2010) Epigallocatechin-3-gallate protects Na + channels in rat ventricular myocytes against sulfite. Cardiovasc Toxicol 10:166–173

    Article  PubMed  CAS  Google Scholar 

  56. Alshatwi AA, Al Obaaid MA, Al Sedairy SA, Al-Assaf AH, Zhang JJ, Lei KY (2010) Tomato powder is more protective than lycopene supplement against lipid peroxidation in rats. Nutr Res 30:66–73

    Article  PubMed  CAS  Google Scholar 

  57. Bose KS, Agrawal BK (2007) Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate and lipid profile in coronary heart disease. Singapore Med J 48:415–420

    PubMed  CAS  Google Scholar 

  58. Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629

    Article  PubMed  CAS  Google Scholar 

  59. Gao W, Pu Y, Luo KQ, Chang DC (2001) Temporal relationship between cytochrome c release and mitochondrial swelling during UV-induced apoptosis in living HeLa cells. J Cell Sci 114:2855–2862

    PubMed  CAS  Google Scholar 

  60. Perry EK, Curtis M, Dick DJ, Candy JM, Atack JR, Bloxham CA, Blessed G, Fairbairn A, Tomlinson BE, Perry RH (1985) Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 48:413–421

    Article  PubMed  CAS  Google Scholar 

  61. Melo JB, Agostinho P, Oliveira CR (2003) Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci Res 45:117–127

    Article  PubMed  CAS  Google Scholar 

  62. Pillay R, Maharaj DS, Daniel S, Daya S (2003) Acetylcholine reduces cyanide-induced superoxide anion generation and lipid peroxidation in rat brain homogenates. Prog Neuropsychopharmacol Biol Psychiatry 27:61–64

    Article  PubMed  CAS  Google Scholar 

  63. van Laar T, De Deyn PP, Aarsland D, Barone P, Galvin JE (2010) Effects of cholinesterase inhibitors in Parkinson’s disease dementia: a review of clinical data. CNS Neurosci Ther [Epub ahead of print]

  64. Gabelli C (2003) Rivastigmine: an update on therapeutic efficacy in Alzheimer’s disease and other conditions. Curr Med Res Opin 19:69–82

    PubMed  CAS  Google Scholar 

  65. Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT (2009) A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 34:279–290

    Article  PubMed  CAS  Google Scholar 

  66. McNamara P, Durso R, Harris E (2007) “Machiavellianism” and frontal dysfunction: evidence from Parkinson’s disease. Cogn Neuropsychiatry 12:285–300

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the financial assistance received from the Department of Science of Technology and the University Grants Commission under the PURSE and SAP programs.

Conflict of interest

There is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Panjab University, Basic Medical Science Building, Chandigarh, 160014, India

    Harpreet Kaur, Shaveta Chauhan & Rajat Sandhir

Authors
  1. Harpreet Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaveta Chauhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rajat Sandhir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajat Sandhir.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaur, H., Chauhan, S. & Sandhir, R. Protective Effect of Lycopene on Oxidative Stress and Cognitive Decline in Rotenone Induced Model of Parkinson’s Disease. Neurochem Res 36, 1435–1443 (2011). https://doi.org/10.1007/s11064-011-0469-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0469-3

Keywords

Search

Navigation