Intake of Tomato-Enriched Diet Protects from 6-Hydroxydopamine-Induced Degeneration of Rat Nigral Dopaminergic Neurons
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.
KeywordsDiet Dopamine Lycopene Parkinson’s disease Striatum β-carotene
Analysis of variance
Cauliflower mosaic virus 35S
High performance liquid chromatography
Liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry
Protected least significance difference
Reactive oxygen species
Substantia nigra pars compacta
Tomato lycopene β-cyclase.
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.
- Brooks DJ (1998) The early diagnosis of Parkinson’s disease. Ann Neurol 44(Suppl):S19–S31Google 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 1168:90–96CrossRefPubMedGoogle Scholar
- Jellinger K (1989) Pathology of Parkinson’s disease. In: Calne DB (ed) Handbook of experimental pharmacology, vol 8. Springer, Berlin, pp 47–112Google 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), 461.14Google Scholar
- Nagao A (2004) Oxidative conversion of carotenoids to retinoids and other products. J Nutr 134:273S–240SGoogle Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, New YorkGoogle 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 85:749–754CrossRefPubMedGoogle 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 78:367–371CrossRefPubMedGoogle Scholar