Skip to main content
SpringerLink
Log in

Intake of Tomato-Enriched Diet Protects from 6-Hydroxydopamine-Induced Degeneration of Rat Nigral Dopaminergic Neurons

  • Chapter
  • First Online:
Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 73))

Abstract

There is extensive evidence that oxidative damage of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) may contribute to the pathogenesis of Parkinson’s disease (PD). We evaluated the potential neuroprotective effect of diets enriched with wild-type Red Setter (RS) tomato or transgenic High Carotene (HC) tomato, rich in β-carotene, obtained by the activation of lycopene β-cyclase (tlcy-b), in an animal model of PD. Male Fischer 344 rats were fed for 14 days with standard AltrominMT diet, 5% RS- or 5% HC-enriched diet. Seven days after the beginning of this diet regimen, the rats were lesioned by 6-hydroxydopamine (6-OHDA) injected into the left SNc. After further 7 days, the rats were sacrificed, and DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in both the left (ipsilateral) and the right (contralateral) striata were measured. Striatal DA levels were reduced by 86.5 ± 5.0% in control, 86.2 ± 5.0% in HC-, and 56.0 ± 9.0% in RS-fed group. Striatal DOPAC was decreased by 85.6 ± 5.0% in controls, 83.0 ± 6.0% in HC-, and 58.9 ± 10.0% in RS-fed group. Blood was obtained from the rats on day 14 and the plasma level of licopene and β-carotene was measured by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) for the determination of lycopene and β-carotene levels. The plasma level of lycopene was 4.7 ± 0.2 ng/ml in 5% RS-fed rats, while it was undetectable (< 2.5 ng ml−1) in control and HC-fed rats. The efficacy of RS diet to preserve striatal dopaminergic innervation can be attributed to the ability of lycopene to prevent the degeneration of DA-containing neurons in the SNc.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

6-OHDA:

6-hydroxydopamine

ANOVA:

Analysis of variance

BHT:

Butylated hydroxytoluene

CaMV25S:

Cauliflower mosaic virus 35S

DA:

Dopamine

DOPAC:

3,4-dihydroxyphenylacetic acid

GSH:

Glutathione

HC:

High carotene

HPLC:

High performance liquid chromatography

LC-APCI-MS:

Liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD:

Parkinson’s disease

PLSD:

Protected least significance difference

ROS:

Reactive oxygen species

RS:

Red Setter

SNc:

Substantia nigra pars compacta

tlcy-b :

Tomato lycopene β-cyclase.

References

  • Al-Babili S, Beyer P (2005) Golden Rice-five years on the road-five years to go? Trends Plant Sci 10:565–73

    Article  CAS  PubMed  Google Scholar 

  • Barak Y, Wohl Y, Greenberg Y, Bar Dayan Y, Friedman T, Shoval G, Knobler HY (2005) Affective psychosis following Accutane (isotretinoin) treatment. Int Clin Psychopharmacol 20:39–41

    Article  PubMed  Google Scholar 

  • Blum D, Torch S, Lambeng N, Nissou M-F, Benabid A-L, Sadoul R, Verna J-M (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 65:135–172

    Article  CAS  PubMed  Google Scholar 

  • Bremner JD, McCaffey P (2008) The neurobiology of retinoic acid in affective disorders. Prog NeuroPsychopharmacol Biol Psychiatry 32:315–331

    Article  CAS  PubMed  Google Scholar 

  • Brooks DJ (1998) The early diagnosis of Parkinson’s disease. Ann Neurol 44(Suppl):S19–S31

    Google Scholar 

  • Carta M, Stancapiano R, Tronci E, Collu M, Usiello A, Morelli M, Fadda F (2006) Vitamin A deficiency induces motor impairements and striatal cholinergic dysfunction in rats. Neuroscience 139: 1163–1172

    Article  CAS  PubMed  Google Scholar 

  • D’Ambrosio C, Giorio G, Marino I, Merendino A, Petrozza A, Salfi L, Stilliani AL, Cellini F (2004) Virtually complete conversion of lycopene into β-carotene in fruits of tomato plants transformed with the tomato lycopene β-cyclase (tlcy-b) cDNA. Plant Science 166:207–214

    Article  Google Scholar 

  • Dawson TM, Dawson VL (2002) Neuroprotective and neurorestorative strategies for Parkinson's disease. Nat Neurosci 5:S1058–S1061

    Article  Google Scholar 

  • Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells SE, Jenner P, Marsden C (1991) Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain 114:1953–1975

    Article  PubMed  Google Scholar 

  • Dexter DT, Holley AE, Flitter WD, Slater TF, Wells FR, Daniel S, Lees AJ, Marsden CD (1994) Increased levels of lipid hydroperoxides in the Parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord 9:92–97

    Article  CAS  PubMed  Google Scholar 

  • Di Giovanni G (2008) Will it be possible to prevent nigral neurodegeneration? CNS Neurol Disord Drug Targets 7:28–44

    Article  PubMed  Google Scholar 

  • Di Matteo V, Pierucci M, Di Giovanni G, Di Santo A, Poggi A, Benigno A, Esposito E (2006a) Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study. Brain Res 1095:167–177

    Article  PubMed  Google Scholar 

  • Di Matteo V, Benigno A, Pierucci M, Giuliano DA, Crescimanno G, Esposito E, Di Giovanni G (2006b) 7-nitroindazole protects striatal dopaminergic neurons against MPP+-induced degeneration: an in vivo microdialysis study. Ann NY Acad Sci 1089:462–471

    Article  PubMed  Google Scholar 

  • Ebadi M, Srinivasan SK, Baxi MD (1996) Oxidative stress and antioxidant therapy in Parkinson’s disease. Progr Neurobiol 48:1–19

    Article  CAS  Google Scholar 

  • Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S (2002) A review of specific antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 23:719–735

    Article  CAS  PubMed  Google Scholar 

  • Esposito E, Capasso M, di Tomasso N, Corona C, Pellegrini F, Uncini A, Vitaglione P, Fogliano V, Piantelli M, Sensi SL (2007) Antioxidant strategies based on tomato-enriched food or pyruvate do not affect disease onset and survival in an animal model of amyotrophic lateral sclerosis. Brain Res 1168:90–96

    Article  CAS  PubMed  Google Scholar 

  • Fahn S (1991) An open trial of high-dosage antioxidants in early Parkinson’s disease. Am J Clin Nutr 53:380S–382S

    CAS  PubMed  Google Scholar 

  • Fall PA, Fredrikson M, Axelson O, Granérus AK (1999) Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden. Mov Disord 14:28–37

    Article  CAS  PubMed  Google Scholar 

  • Fearnley JM, Lees AJ (1991) Ageing and Parkinson's disease: SNc regional selectivity. Brain 114:2283–2301

    Article  PubMed  Google Scholar 

  • Ferguson SA, Cisneros FJ, Gough BJ, Ali SF (2005) Four weeks of oral isotretinoin treatment causes few signs of general toxicity in male and female Sprague-Dawley rats. Food Chem Toxicol 43:1289–1296

    Article  CAS  PubMed  Google Scholar 

  • Ferreira AL, Yeum K-J, Liu C, Smith D et al (2000) Tissue distribution of lycopene in ferrets and rats after lycopene supplementation. J Nutr 130:1256–60

    CAS  PubMed  Google Scholar 

  • Goodman AB (1998) Three independent lines of evidence suggest retinoids as causal to schizophrenia. Proc Natl Acad Sci USA 95:7240–7244

    Article  CAS  PubMed  Google Scholar 

  • Goodman DS, Huang HS (1965) Biosynthesis of vitamin A with rat intestinal enzymes. Science 149:879–880

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. Trends Neurosci 6:22–26

    Article  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Jellinger K (1989) Pathology of Parkinson’s disease. In: Calne DB (ed) Handbook of experimental pharmacology, vol 8. Springer, Berlin, pp 47–112

    Google Scholar 

  • Jenner P, Dexter DT, Sian J, Schapira AHV, Marsden CD (1992) Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incident Lewy body disease. Ann Neurol 32:582–587

    Article  Google Scholar 

  • Krezel W, Ghyselinck N, Samad TA, Dupé V, Kastner P, Borrelli E, Chambon P (1998) Impaired locomotion and dopamine signaling in retinoid receptor mutant mice. Science 279:863–867

    Article  CAS  PubMed  Google Scholar 

  • Lang AE, Lozan AM (1998) Parkinson’s disease first of two parts. New Engl J Med 339:1044–1053

    Article  CAS  PubMed  Google Scholar 

  • Mabrouk OS, Roth BL, Sivagnaniar I, Pehek EA (2003) Vitamin A derivative 13-cis retinoic acid (Accutane) modulates stress induced dopamine release in the rat medial prefrontal cortex. Society for Neuroscience Abstracts (2003 Abstract Viewer/Itinerary Planner), 461.14

    Google Scholar 

  • Mattson MP, Chan SL, Duan W (2002) Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev 82:637–672

    CAS  PubMed  Google Scholar 

  • Nagao A (2004) Oxidative conversion of carotenoids to retinoids and other products. J Nutr 134:273S–240S

    Google Scholar 

  • Nguyen ML, Schwartz SJ (1998) Lycopene stability during food processing. Proc Soc Exp Biol Med 218:101–105

    CAS  PubMed  Google Scholar 

  • Olson JA, Hayaisshi O (1965) The enzymatic cleavage of β-carotene into vitamin A by soluble enzymes of rat liver and intestine. Proc Natl Acad Sci USA 54:1364–1370

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  • Perry TL, Yong VW, Hansen S, Jones K, Bergeron C, Foulks JG, Wright JM (1987) α-Tocopherol and β-carotene do not protect marmosets against the dopaminergic neurotoxicity of N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. J Neurol Sci 81:321–331

    Article  CAS  PubMed  Google Scholar 

  • Rao AV, Agarwal S (2000) Role of antioxidant lycopene in cancer and heart disease. J Am Coll Nutr 19:563–569

    CAS  PubMed  Google Scholar 

  • Rao AV, Balachandran B (2002) Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci 5:291–309

    Article  CAS  PubMed  Google Scholar 

  • Rao AV (2004) Processed tomato products as a source of dietary lycopene: bioavailability and antioxidant properties. Can J Diet Pract Res 65:161–165

    Article  PubMed  Google Scholar 

  • Ribaya-Mercado JD, Holmgren SC, Fox JG, Russell RM (1989) Dietary β-carotene absorption and metabolism in ferrets and rats. J Nutr 119:665–668

    CAS  PubMed  Google Scholar 

  • Riso P, Visioli F, Erba D, Testolin G, Porrini M (2004) Lycopene and vitamin C concentrations increase in plasma and lymphocytes after tomato intake. Effect on cellular antioxidant protection. Eur J Clin Nutr 58:1350–1358

    Article  CAS  PubMed  Google Scholar 

  • Rissanen TH, Voutilainen S, Nyyssonen K, Lakka TA, Sivenius J, Salonen R, Kaplan GA, Salonen JT (2001) Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Hearth Disease Risk Factor Study. Br J Nutr 85:749–754

    Article  CAS  PubMed  Google Scholar 

  • Saga Y, Kobayashi M, Ohta H, Murai N, Nakai N, Oshima M, Taketo MM (1999) Impaired extrapyramidal function caused by the targeted disruption of retinoid receptor RXRγ1 isoform. Genes Cells 4:219–228

    Article  CAS  PubMed  Google Scholar 

  • Samad TA, Krezel W, Chambon P, Borrelli E (1997) Regulation of dopaminergic pathway by retinoids: Activation of D2 receptor promoter by members of the retinoic acid receptor-retinoid X receptor family. Proc Natl Acad Sci USA 94:14349–14354

    Article  CAS  PubMed  Google Scholar 

  • Scherman D, Desnos C, Darchen F, Pollak P, Javoy-Agid F, Agid Y (1989) Striatal dopamine deficiency in Parkinson's disease: role of aging. Ann Neurol 26:551–557

    Article  CAS  PubMed  Google Scholar 

  • Simonian NA, Coyle JT (1996) Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 36:83–106

    Article  CAS  PubMed  Google Scholar 

  • Suganuma H, Hirano T, Arimoto Y, Inakuma T (2002) Effect of tomato intake on striatal monoamine level in a mouse model of experimental Parkinson’s disease. J Nutr Sci Vitaminol 48:251–254

    CAS  PubMed  Google Scholar 

  • Talalay P (2000) Chemoprotection against cancer by induction of phase 2 enzyme. Biofactors 12:5–11

    Article  CAS  PubMed  Google Scholar 

  • Veldink JH, Kalmijn S, Groeneveld GJ, Wunderink W, Koster A, de Vries JH, van der Luyt J, Wokke JH, Van den Berg LH (2007) Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 78:367–371

    Article  CAS  PubMed  Google Scholar 

  • von Bohlen und Halbach O, Schober A, Krieglstein K (2004) Genes, proteins, and neurotoxins involved in Parkinson’s disease. Prog Neurobiol 73:151–177

    Article  Google Scholar 

  • Zetterström RH, Lindqvist E, de Urquiza AM, Tomac A, Eriksson U, Perlmann T, Olson L (1999) Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid. Eur J Neurosci 11: 407–416

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study has been carried out in the frame of a MIUR L.297/96-financed project (SAFE) to Agrobios Metapontum. We thank Dr. Francesco Cellini and Dr. Angelo Petrozza, Agrobios Metapontum for kindly supplying RS and HC tomatoes and Dr. Gianluigi Forloni, Mario Negri Institute for Pharmacological Research, for the helpful discussion.

Author information

Authors and Affiliations

  1. Istituto di Ricerche Farmacologiche “Mario Negri”, Consorzio “Mario Negri” Sud, 66030, Santa Maria Imbaro, CH, Italy

    Vincenzo di Matteo, Massimo Pierucci, Luana Katia Dragani, Stefania Murzilli, Andreina Poggi & Ennio Esposito

  2. Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana “G. Pagano”, Università degli Studi di Palermo, 90134, Palermo, Italy

    Giuseppe Di Giovanni

Authors
  1. Vincenzo di Matteo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Massimo Pierucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppe Di Giovanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luana Katia Dragani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefania Murzilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andreina Poggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ennio Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincenzo di Matteo .

Editor information

Editors and Affiliations

  1. Fac. Medicina e Chirurgia, Università di Palermo, Corso Tukory 129, Palermo, 90134, Italy

    Giuseppe Giovanni

  2. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Vincenzo Di Matteo

  3. Mario Negri, Istituto di Ricerche Farmacologiche, Via Nazionale 8, Santa Maria Imbaro, 66030, Italy

    Ennio Esposito

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag/Wien Printed in Germany

About this chapter

Cite this chapter

di Matteo, V. et al. (2009). Intake of Tomato-Enriched Diet Protects from 6-Hydroxydopamine-Induced Degeneration of Rat Nigral Dopaminergic Neurons. In: Giovanni, G., Di Matteo, V., Esposito, E. (eds) Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra. Journal of Neural Transmission. Supplementa, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-211-92660-4_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-92660-4_28

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-92659-8

  • Online ISBN: 978-3-211-92660-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation