Objective: This study investigated into the ef-fect of lycopene on expression of APP, bax and bcl-2 in hippocampal CA1 region of rats with hyperlipidemia. Methods: By total cholesterol (TC) and body weight, 48 adult male SD rats were randomized into six groups, a normal control group, fed with basic feed; a high-fat model group, fed with high-fat feed; a positive drug control group, fed with high-fat feed and administrated with fluvastatin sodium at a dose of 10 mg?kg?bw-1?d-1 by gastric perfusion; and lycopene groups at three dose levels, fed with high-fat feed and administrated with lycopene at doses of 11, 22 and 44 mg?kg?bw-1?d-1 respec-tively also by gastric perfusion. Caudal venous blood samples of rats in all groups were taken at week 0, week 1 and week 3 after the experiment started so as to assay TC, TG, LDL-C and HDL-C; at the end of the experiment, rat brains were taken and sections of the hippocampal CA1 re-gion were prepared. Expression of APP, bax and bcl-2 in the CA1 region was determined by im-munohistochemical methods and morphologi-cal examination was carried out. Results: One week after fed with high-fat feed, models of hy-perlipidemia rats were established; at the end of experiment, hippocampal APP and bax expres-sion was enhanced while bcl-2 expression was significantly weakened (p<0.05); to rats with hyperlipidemia, both lycopene and fluvastatin sodium could reduce TC, TG and LDL-C, inhibit expression of hippocampal APP and bax and promote expression of bcl-2 (p<0.05). Conclu- sion: Lycopene down-regulates the expression of bax and up-regulates that of bcl-2 mainly by reducing serum TC and LDL-C and weakening expression of APP in the hippocampal CA1 re-gion of rats with hyperlipidemia, thereby main-taining normal morphology of hippocampal neurons and facilitating the protection of the brain.
S. Agarwal and A. V. Rao, (2000) Tomato lycopene and its role in human health and chronic diseases, CMAJ, 163, 739-744.
T. H. Rissanen, S. Voutilainen, K. Nyyssonen, R. Sa-lonen, G. A. Kaplan, and J. T. Salonen, (2003) Serum lycopene concentrations and carotid atherosclerosis: The Kuopio ischaemic heart disease risk factor study, Am JClin Nutr, 77, 133-138.
K. Canene-Adams, J. K. Campbell, S. Zaripheh, E. H. Jeffery, and J. W. Erdman Jr., (2005) The tomato as a functional food, J Nutr, 135, 1226-1230.
A. O. Omoni and R. E. Aluko, (2005) The anti-carcino-genic and anti-atherogenic effects of copene: A review, Trends Food Sci Tech, 16, 344-350.
K. Klipstein-Grobushch, L. J. Launer, J. M. Geleijnse, H. Boeing, A. Hofman, and J. C. Witteman, (2000) Serum carotenoids and atherosclerosis, The Rotterdam Study. Atherosclerosis, 148, 49-56.
T. Rissanen, S. Voutilainen, K. Nyyssonen, R. Salonen, G. A. Kaplan, and J. T. Salonen, (2003) Serum lycopene concentration and carotid atherosclerosis: The Kuopio ischaemic heart disease risk factor study, Am. J. Clin. Nutr, 77, 133-138.
M. Y. Hu, Y. L. Li, Z. Q. Liu, S. L. Ou, Y. M. Huang, (2007) The protective effect of lycopene on atherogene-sis in rabbits, Acta Nutrimenta Sinica, 29, 498-502.
M. Y. Hu, Y. L. Li, C. H. Jiang, Z. Q. Liu, S. L. Qu, Y. M. Huang, (2008) Comparison of lycopene and fluvas-tatin effects on atherosclerosis induced by a high-fat diet in rabbits, Nutrition, 24, 1030-1038.
S. Bodovitz and W. L. Klein, (1996) Cholesterol modu-lates alpha-secretase cleavage of amyloid precursor pro-tein, J Biol Chem, 21, 4436-4440.
M. Kivipelto, E. L. Helkala, M. P. Laakso, T. H?nninen, M. Hallikainen, K. Alhainen, H. Soininen, J. Tuomilehto, and A. Nissinen, (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study, BMJ, 322, 1447-1451.
K. Sleegers, N. Brouwers, I. Gijselinck, J. Theuns, D. Goossens, J. Wauters, J. Del-Favero, M. Cruts, C. M. van Duijn, and C. van Broeckhoven, (2006) APP duplication is sufficient to cause early onset Alzheimer’s dementia with cerebral amyloid angiopathy. Brain, 129, 2977-2983.
A. V. Rao and L. G. Rao, (2007) Carotenoids and human health, Pharmacological Research, 55, 207-216.
C. K. Jain, S. Agarwal, and A. V. Rao, (1999) The effect of dietary lycopene on bioavailability, tissue distribution, in vivo antioxidant properties and colonic preneoplasia in rats, Nutrihon Research, 19, 1383-1391.
C. J. Foy, A. P. Passmore, M. D. Vahidassr, I. S. Young, and J. T. Lawson, (1999) Plasma chain-breaking antioxi-dants in Alzheimer’s disease, vascular dementia and Parkinson’s disease, Q JM, 92, 39-45.
P. R. Deepa and T. P. Varalakshmi, (2004) Atheropro-tective effect of exogenous heparin-derivative treatment on the aortic disturbances and lipoprotein oxidation in hypercholesterolemic diet fed rats, Clinica Chimica Acta, 12, 119-130.
F. Quang, B. -J. Lee, W. Lee, and H. -K. Han, (2009) Pharmacokinetic drug interaction between fexofenadine and fluvastatin mediated by organic anion-transporting polypeptides in rats, European Journal of Pharmaceutical Sciences.
M. Itagaki, A. Takaguri, S. Kano, S. Kaneta, K. Ichihara, and K. Satoh, (2009) Possible mechanisms underlying statin-induced skeletal muscletoxicity in L6 fibroblasts and in rats, J Pharmacol Sci, 109, 94-101.
T. D. Watson, R. F. Butterwick, M. McConnell, and P. J. Markwell, (1995) Development of methods for analyzing plasma lipoprotein concentrations and associated enzyme activities and their use to measure the effects of preg-nancy and lactation in cats, Am J Vet Res, 56, 289-296.
W. T. Friedewald, R. I. Levy, and D. S. Fredrickson, (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge, Clin Chem, 18, 499-502.
(2008) Acceleration of diabetic wound healing withchi-tosan-crosslinked collagen sponge containing recombi-nant human acidic fibroblast growth factor inhealing- impaired STZ diabetic rats, Life Sciences, 82, 190-204.
S. H. Peng, H. Deng, D. Y. Feng, and H. Zheng, (2004) Expression of HSP 70 and caspase 3 and their signifi-cance in hepatocellular carcinoma tissues, World Chinese Journal of Digestology, 12, 782-784.
L. J. Launer, L. R. White, H. Petrovitch, G. W. Ross, and J. D. Curb, (2001) Cholesterol and neuropathologic markers of AD: A population2-based autopsy study, Neurology, 57, 1447-1452.
L. Puglielli, R. E. Tanzi, and D. M. Kovacs, (2003) Alz-heimer’s disease: The cholesterol connection, Nat Neu-rosci, 6, 345-351.
M. Burns and K. Duff, (2002) Cholesterol in Alzheimer’s disease and Tauopathy, Ann N Y Acad Sci, 977, 367- 375.
K. Yanagisawa, (2002) Cholesterol and pathological processes in Alzheimer’s disease, J Neurosci Res, 70, 361-366.
A. E. Roher, Y. M. Kuo, K. M. Kokjohn, M. R. Emmerling, S. Gracon, (1999) Amyloid and lipids in the pathology of Alzheimer’s disease, Amyloid, 6, 136-145.
G. Lesser, K. Kandiah, L. S. Libow, A. Likourezos, B. Breuer, D. Marin, R. Mohs, V. Haroutunian, and R. Neufeld, (2001) Elevated serum total and LDL choles-terol in very old patients with Alzheimer’s disease, De-ment Geriatr Cogn Disord, 12, 138-145.
W. G. Wood, G. P. Eckert, U. Igbavboa, and W. E. Müller, (2003) Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alz-heimer’s disease, Biochim Biophys Acta, 1610, 281-290.
P. P. Zandi, D. L. Sparks, A. S. Khachaturian, J. Tschanz, M. Norton, M. Steinberg, K. A. Welsh-Bohmer, and J. C. Breitner, (2005) Cache county study investigators: do statins reduce risk of incident dementia and Alzheimer disease? The cache county study, Arch Gen Psychiatry, 62, 217-224.
C. Kirsch, G. P. Eckert, A. R. Koudinov, and W. E. Müller, (2003) Brain cholesterol, statins and Alzheimer’s disease, Pharmacopsychiatry, 36, S113-119.
I. Masse, R. Bordet, D. Deplanque, A. Al Khedr, F. Rich-ard, C. Libersa, and F. Pasquier, (2005) Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease, Neurol Neurosurg Psychistry, 76, 1624-1629.
J. Marx, (2001) Alzheimer’s disease: BAD for the heart, BAD for the mind, Science, 294, 508-509.
A. Delacourte, (2006) From physiopathology to treat-ment of Alzheimer’s disease, Rev Neurol (Paris), 162, 909-912.
G. Verdile, S. Fuller, C. S. Atwood, S. M. Laws, S. E. Gandy, and R. N. Martins, (2004) The role of beta amy-loid in Alzheimer’s disease: Still a cause of everything or the only one who got caught, Pharmacol Res, 50, 397-409.
D. L. Sparks, S. W. Scheff, J. C. Hunsaker 3rd, H. Liu, T. Landers, D. R. Gross, (1994) Induction of Alzheimer-like β-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol, Exp Neurol, 126, 88-94.
D. L. Sparks, Y. M. Kuo, A. Roher, T. Martin, R. J. Lukas, (2000) Alterations of Alzheimer’s disease in the cholesterol-fed rabbit, including vascular inflammation, Preliminary Observations Ann N Y Acad Sci, 903, 335-344.
L. Li, D. Cao, D. W. Garber, H. Kim, and K. Fukuchi, (2003) Association of aortic atherosclerosis with cerebral beta- amyloidosis and learning deficits in a mouse model of Alzheimer’s disease, Am J Pathol, 163, 2155-2161.
M. Simons, P. Keller, B. De Strooper, K. Beyreuther, C. G. Dotti, and K. Simons, (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons, Neurobiology, 95, 6460-6464.
L. Conboy, K. J. Murphy, and C. M. Regan, (2005) Amyloid precursor protein expression in the rat hippo-campal dentate gyrus modulates during memory con-solidation, J Neurochem., 95, 1677-1688.
J. Hardy and D. J. Selkoe, (2002) The amyloid hypothe-sis of Alzheimer’s disease: progress and problems on the road to therapeutics, Science, 297, 353-356.
F. S. Shie, L. W. Jin, D. G. Cook, J. B. Leverenz, and R. C. LeBoeuf, (2002) Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice, Neuroreport, 13, 455-459.
A. Rovelet-Lecrux, D. Hannequin, G. Raux, N. Le Meur, A. Laquerrière, A. Vital, C. Dumanchin, S. Feuillette, A. Brice, M. Vercelletto, F. Dubas, T. Frebourg, D. Cam-pion, (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy, Nat Genet, 38, 24-26.
P. N. Shevtsov, E. F. Shevtsova, G. S. Burbaeva, S. O. Bachurin, (2006) Disturbed assembly of human cerebral mierotubules in Alzheimer’s disease, Bull Exp Biol Med, 141, 265-268.
A. Fuso, I. Seminara, R. A. Cavallaro, F. D’Anselmi, S. Scarpa, (2005) S-aden0sylmethi0nine/homocysteine cy-cle alterations modify DNA methylation status with con-sequent deregulation of PSI and BACE and beta-amyloid production, Mol Cell Neurosci, 28, 195-204.
E. B. Beeker and A. Bonni, (2004) Cell cycle regulation of neuronal apoptosis in development and disease, Pmg Neumbiol, 72, 1-6.
S. H. Graham and J. Chen, (2001) Programmed cell death in cerebral ischemia, J Cereb Blood Flow Metab, 2l, 99-109.
A. C. Leblane, (2005) The role of apoptotic pathways in Alzheimer’s disease neumdegeneration and cell death, Curr Alzheimer Res, 2, 389-397.
W. P. Li, W. Y. Chan, H. W. Lai, and D. T. Yew, (1997) Terminal DUTP nick end labeling (TUNEL) positive cells in the different regions of the brain in normal aging and Alzheimer patients, Mol Neurosci, 8, 75-82.
S. Shimohama, (2000) Apoptosis in Alzheimer’s disease an update, Apoptosis, 5, 9-16.
S. Shimohama, H. Tanino, and S. Fujimoto, (1999) Changes in caspase expression in Alzheimer’s disease, comparison with development and aging, Biochem Bio-phys Res Commun, 256, 381-384.
F. J. Antonawich, H. J. Federoff, and J. N. Davis, (1999) BCL-2 transduction, using a herpes simplex virus am-plicon, protects hippocampal neurons from transient global ischemia, Exp Neurol, 156, 130-137.
E. ParADis, H. Douillard, M. Koutroumanis, C. Goodyer, and A. LeBlanc, (1996) Amyloid beta peptide of Alzheimer’s diseased down regulates Bcl-2 and up regulates Bax expres-sion in human neurons, Neurosis, 16, 7533- 7539.