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NeuroMolecular Medicine

Erschienen in:

01.03.2014 | Original Paper

Curcumin Nanoparticles Attenuate Neurochemical and Neurobehavioral Deficits in Experimental Model of Huntington’s Disease

verfasst von: Rajat Sandhir, Aarti Yadav, Arpit Mehrotra, Aditya Sunkaria, Amandeep Singh, Sadhna Sharma

Erschienen in: NeuroMolecular Medicine | Ausgabe 1/2014

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Abstract

Till date, an exact causative pathway responsible for neurodegeneration in Huntington’s disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.

Abu-Taweel, G. M., Ajarem, J. S., & Ahmad, M. (2013). Protective effect of curcumin on anxiety, learning behaviour, neuromuscular activities, brain neurotransmitters and oxidative stress enzymes in cadmium intoxicated mice. Journal of Behavioral and Brain Sciences, 3, 74–84.CrossRef

Alexi, T., Hughes, P. E., Faull, R. L., & Williams, C. E. (1998). 3-Nitropropionic acid’s lethal triplet: Cooperative pathways of neurodegeneration. NeuroReport, 9(11), R57–R64.CrossRefPubMed

Al-Omar, F. A., Nagi, M. N., Abdulgadir, M. M., Al Joni, K. S., & Al-Majed, A. A. (2006). Immediate and delayed treatments with curcumin prevents forebrain ischemia-induced neuronal damage and oxidative insult in the rat hippocampus. Neurochemical Research, 31(5), 611–618.CrossRefPubMed

Alston, T. A., Mela, L., & Bright, H. J. (1977). 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proceedings of the National Academy of Sciences, USA, 74(9), 3767–3771.CrossRef

Bharath, S., Hsu, M., Kaur, D., Rajagopalan, S., & Andersen, J. K. (2002). Glutathione, iron and Parkinson’s disease. Biochemical Pharmacology, 64(5–6), 1037–1048.CrossRefPubMed

Bizat, N., Hermel, J. M., Boyer, F., Jacquard, C., Creminon, C., Ouary, S., et al. (2003). Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate: Implications for Huntington’s disease. Journal of Neuroscience, 23(12), 5020–5030.PubMed

Bogdanov, M. B., Ferrante, R. J., Kuemmerle, S., Klivenyi, P., & Beal, M. F. (1998). Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington’s disease. Journal of Neurochemistry, 71(6), 2642–2644.CrossRefPubMed

Boissier, J. R., & Simon, P. (1965). Action of caffeine on the spontaneous motility of the mouse. Archives Internationales de Pharmacodynamie et de Therapie, 158(1), 212–221.PubMed

Brouillet, E., Guyot, M. C., Mittoux, V., Altairac, S., Conde, F., Palfi, S., et al. (1998). Partial inhibition of brain succinate dehydrogenase by 3-nitropropionic acid is sufficient to initiate striatal degeneration in rat. Journal of Neurochemistry, 70(2), 794–805.CrossRefPubMed

Browne, S. E., Bowling, A. C., MacGarvey, U., Baik, M. J., Berger, S. C., Muqit, M. M., et al. (1997). Oxidative damage and metabolic dysfunction in Huntington’s disease: Selective vulnerability of the basal ganglia. Annals of Neurology, 41(5), 646–653.CrossRefPubMed

Browne, S. E., Ferrante, R. J., & Beal, M. F. (1999). Oxidative stress in Huntington’s disease. Brain Pathology, 9(1), 147–163.CrossRefPubMed

Chan, D. C. (2006). Mitochondria: Dynamic organelles in disease, aging, and development. Cell, 125(7), 1241–1252.CrossRefPubMed

Cheng, A. L., Hsu, C. H., Lin, J. K., Hsu, M. M., Ho, Y. F., Shen, T. S., et al. (2001). Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Research, 21(4B), 2895–2900.

Cirillo, G., Maggio, N., Bianco, M. R., Vollono, C., Sellitti, S., & Papa, M. (2010). Discriminative behavioral assessment unveils remarkable reactive astrocytosis and early molecular correlates in basal ganglia of 3-nitropropionic acid subchronic treated rats. Neurochemistry International, 56(1), 152–160.CrossRefPubMed

Dhillon, N., Aggarwal, B. B., Newman, R. A., Wolff, R. A., Kunnumakkara, A. B., Abbruzzese, J. L., et al. (2008). Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinical Cancer Research, 14(14), 4491–4499.CrossRefPubMed

Duran-Vilaregut, J., Manich, G., Del Valle, J., Camins, A., Pallas, M., Vilaplana, J., et al. (2012). Expression pattern of ataxia telangiectasia mutated (ATM), p53, Akt, and glycogen synthase kinase-3beta in the striatum of rats treated with 3-nitropropionic acid. Journal of Neuroscience Research, 90(9), 1803–1813.CrossRefPubMed

Fang, M., Jin, Y., Bao, W., Gao, H., Xu, M., Wang, D., et al. (2012). In vitro characterization and in vivo evaluation of nanostructured lipid curcumin carriers for intragastric administration. International Journal of Nanomedicine, 7, 5395–5404.CrossRefPubMedCentralPubMed

Fiske, C. H., & Subbarow, Y. (1925). The colorimetric determination of phosphorus. Journal of Biological Chemistry, 66, 375–400.

Forsmark-Andree, P., Lee, C. P., Dallner, G., & Ernster, L. (1997). Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Radical Biology and Medicine, 22(3), 391–400.CrossRefPubMed

Frautschy, S. A., & Cole, G. M. (2009). Bioavailable curcuminoid formulations for treating Alzheimer’s disease and other age-realted disorders. United States. US 2009/0324703 A1.

Gould, T. J., Bowenkamp, K. E., Larson, G., Zahniser, N. R., & Bickford, P. C. (1995). Effects of dietary restriction on motor learning and cerebellar noradrenergic dysfunction in aged F344 rats. Brain Research, 684(2), 150–158.CrossRefPubMed

Green, D. R., & Kroemer, G. (2004). The pathophysiology of mitochondrial cell death. Science, 305(5684), 626–629.CrossRefPubMed

Griffiths, D. E., & Houghton, R. L. (1974). Studies on energy-linked reactions: Modified mitochondrial ATPase of oligomycin-resistant mutants of Saccharomyces cerevisiae. European Journal of Biochemistry, 46(1), 157–167.CrossRefPubMed

Guerrieri, F., Capozza, G., Fratello, A., Zanotti, F., & Papa, S. (1993). Functional and molecular changes in FoF1 ATP-synthase of cardiac muscle during aging. Cardioscience, 4(2), 93–98.PubMed

Guyot, M. C., Hantraye, P., Dolan, R., Palfi, S., Maziere, M., & Brouillet, E. (1997). Quantifiable bradykinesia, gait abnormalities and Huntington’s disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid. Neuroscience, 79(1), 45–56.CrossRefPubMed

Hamilton, B. F., & Gould, D. H. (1987). Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: A type of hypoxic (energy deficient) brain damage. Acta Neuropathologica, 72(3), 286–297.CrossRefPubMed

Hayes, J. D., & McMahon, M. (2001). Molecular basis for the contribution of the antioxidant responsive element to cancer chemoprevention. Cancer Letters, 174(2), 103–113.CrossRefPubMed

Henderson, J. M., Schleimer, S. B., Allbutt, H., Dabholkar, V., Abela, D., Jovic, J., et al. (2005). Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism. Behavioural Brain Research, 162(2), 222–232.CrossRefPubMed

Hickey, M. A., Zhu, C., Medvedeva, V., Lerner, R. P., Patassini, S., Franich, N. R., et al. (2012). Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington’s disease. Molecular Neurodegener, 7, 12.CrossRef

Hissin, P. J., & Hilf, R. (1976). A fluorometric method for determination of oxidized and reduced glutathione in tissues. Analytical Biochemistry, 74(1), 214–226.CrossRefPubMed

Kakkar, V., & Kaur, I. P. (2011). Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food and Chemical Toxicology, 49(11), 2906–2913.CrossRefPubMed

Kakkar, V., Muppu, S. K., Chopra, K., & Kaur, I. P. (2013). Curcumin loaded solid lipid nanoparticles: An efficient formulation approach for cerebral ischemic reperfusion injury in rats. European Journal of Pharmaceutics and Biopharmaceutics, 6411(13), 00059-3.

Kakkar, V., Singh, S., Singla, D., & Kaur, I. P. (2011). Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Molecular Nutrition & Food Research, 55(3), 495–503.CrossRef

King, T. E., & Howard, R. L. (1967). Preparation and properties of soluble NADH dehydrogenase from cardiac muscle. Methods in enzymology (pp. 275–276). New York: Academic Press.

King, T. E., Ohnishi, T., Winter, D. B., & Wu, J. T. (1976). Biochemical and EPR probes for structure-function studies of iron sulfur centers of succinate dehydrogenase. Advances in Experimental Medicine and Biology, 74, 182–227.CrossRefPubMed

Kono, Y. (1978). Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Archives of Biochemistry and Biophysics, 186(1), 189–195.CrossRefPubMed

Kremer, B. (2002). Clinical neurology of Huntington’s disease. OXFORD MONOGRAPHS ON MEDICAL GENETICS.

Kumar, P., & Kumar, A. (2009). Neuroprotective effect of cyclosporine and FK506 against 3-nitropropionic acid induced cognitive dysfunction and glutathione redox in rat: Possible role of nitric oxide. Neuroscience Research, 63(4), 302–314.CrossRefPubMed

Kumar, P., Padi, S. S., Naidu, P. S., & Kumar, A. (2007). Possible neuroprotective mechanisms of curcumin in attenuating 3-nitropropionic acid-induced neurotoxicity. Methods and Findings in Experimental and Clinical Pharmacology, 29(1), 19–25.CrossRefPubMed

Kundu, P., Mohanty, C., & Sahoo, S. K. (2012). Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy. Acta Biomaterialia, 8(7), 2670–2687.CrossRefPubMed

La Fontaine, M. A., Geddes, J. W., Banks, A., & Butterfield, D. A. (2000). 3-Nitropropionic acid induced in vivo protein oxidation in striatal and cortical synaptosomes: Insights into Huntington’s disease. Brain Research, 858(2), 356–362.CrossRefPubMed

Lee, W. T., & Chang, C. (2004). Magnetic resonance imaging and spectroscopy in assessing 3-nitropropionic acid-induced brain lesions: An animal model of Huntington’s disease. Progress in Neurobiology, 72(2), 87–110.CrossRefPubMed

Leventhal, L., Sortwell, C. E., Hanbury, R., Collier, T. J., Kordower, J. H., & Palfi, S. (2000). Cyclosporin A protects striatal neurons in vitro and in vivo from 3-nitropropionic acid toxicity. Journal of Comparative Neurology, 425(4), 471–478.CrossRefPubMed

Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A. G., et al. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods in Enzymology, 186, 464–478.CrossRefPubMed

Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443(7113), 787–795.CrossRefPubMed

Liu, Y., Peterson, D. A., Kimura, H., & Schubert, D. (1997). Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Journal of Neurochemistry, 69(2), 581–593.CrossRefPubMed

Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265–275.PubMed

Miao, W., Hu, L., Scrivens, P. J., & Batist, G. (2005). Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway. Journal of Biological Chemistry, 280(21), 20340–20348.CrossRefPubMed

Mohammadi-Bardbori, A., Bengtsson, J., Rannug, U., Rannug, A., & Wincent, E. (2012). Quercetin, resveratrol, and curcumin are indirect activators of the aryl hydrocarbon receptor (AHR). Chemical Research in Toxicology, 25(9), 1878–1884.CrossRefPubMed

Montoya, A., Price, B. H., Menear, M., & Lepage, M. (2006). Brain imaging and cognitive dysfunctions in Huntington’s disease. Journal of Psychiatry and Neuroscience, 31(1), 21–29.PubMedCentralPubMed

Nasr, P., Carbery, T., & Geddes, J. W. (2009). N-methyl-D-aspartate receptor antagonists have variable affect in 3-nitropropionic acid toxicity. Neurochemical Research, 34(3), 490–498.CrossRefPubMed

Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358.CrossRefPubMed

Petersen, A., Castilho, R. F., Hansson, O., Wieloch, T., & Brundin, P. (2000). Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons. Brain Research, 857(1–2), 20–29.CrossRefPubMed

Pfaffl, M. W., Horgan, G. W., & Dempfle, L. (2002). Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research, 30(9), e36.CrossRefPubMedCentralPubMed

Puka-Sundvall, M., Wallin, C., Gilland, E., Hallin, U., Wang, X., Sandberg, M., et al. (2000). Impairment of mitochondrial respiration after cerebral hypoxia-ischemia in immature rats: relationship to activation of caspase-3 and neuronal injury. Brain Research. Developmental Brain Research, 125(1–2), 43–50.CrossRefPubMed

Ray, B., Bisht, S., Maitra, A., & Lahiri, D. K. (2011). Neuroprotective and neurorescue effects of a novel polymeric nanoparticle formulation of curcumin (NanoCurc) in the neuronal cell culture and animal model: Implications for Alzheimer’s disease. Journal of Alzheimer’s Disease, 23(1), 61–77.PubMedCentralPubMed

Sandhir, R., & Mehrotra, A. (2013). Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: Implications in Huntington’s disease. Biochimica et Biophysica Acta, 1832(3), 421–430.CrossRefPubMed

Sandhir, R., Mehrotra, A., & Kamboj, S. S. (2010). Lycopene prevents 3-nitropropionic acid-induced mitochondrial oxidative stress and dysfunctions in nervous system. Neurochemistry International, 57(5), 579–587.CrossRefPubMed

Sandhir, R., Sood, A., Mehrotra, A., & Kamboj, S. S. (2012). N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington’s disease. Neurodegenerative Diseases, 9(3), 145–157.CrossRefPubMed

Saulle, E., Gubellini, P., Picconi, B., Centonze, D., Tropepi, D., Pisani, A., et al. (2004). Neuronal vulnerability following inhibition of mitochondrial complex II: A possible ionic mechanism for Huntington’s disease. Molecular and Cellular Neuroscience, 25(1), 9–20.CrossRefPubMed

Sharma, S., Zhuang, Y., Ying, Z., Wu, A., & Gomez-Pinilla, F. (2009). Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma. Neuroscience, 161(4), 1037–1044.CrossRefPubMedCentralPubMed

Sottocasa, G. L., Kuylenstierna, B., Ernster, L., & Bergstrand, A. (1967). An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. Journal of Cell Biology, 32(2), 415–438.CrossRefPubMed

Sun, M., Su, X., Ding, B., He, X., Liu, X., Yu, A., et al. (2012). Advances in nanotechnology-based delivery systems for curcumin. Nanomedicine (Lond), 7(7), 1085–1100.CrossRef

Tabrizi, S. J., Cleeter, M. W., Xuereb, J., Taanman, J. W., Cooper, J. M., & Schapira, A. H. (1999). Biochemical abnormalities and excitotoxicity in Huntington’s disease brain. Annals of Neurology, 45(1), 25–32.CrossRefPubMed

Tabrizi, S. J., Workman, J., Hart, P. E., Mangiarini, L., Mahal, A., Bates, G., et al. (2000). Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Annals of Neurology, 47(1), 80–86.CrossRefPubMed

Tedeschi, H., & Harris, D. L. (1958). Some observations on the photometric estimation of mitochondrial volume. Biochimica et Biophysica Acta, 28(2), 392–402.CrossRefPubMed

Towbin, H., Staehelin, T., & Gordon, J. (1992). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Biotechnology, 24, 145–149.PubMed

Tunez, I., Montilla, P., Del Carmen Munoz, M., Feijoo, M., & Salcedo, M. (2004). Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington’s disease. Journal of Pineal Research, 37(4), 252–256.CrossRefPubMed

Wang, H., & Joseph, J. A. (1999). Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radical Biology and Medicine, 27(5–6), 612–616.CrossRefPubMed

Williams, J. N., Jr. (1964). A method for the simultaneous quantitative estimation of cytochromes a, B, C1, and C in mitochondria. Archives of Biochemistry and Biophysics, 107, 537–543.CrossRefPubMed

Wu, J., Li, Q., Wang, X., Yu, S., Li, L., Wu, X., et al. (2013). Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway. PLoS ONE, 8(3), e59843. doi:10.1371/journal.pone.0059843.CrossRefPubMedCentralPubMed

Yang, K. Y., Lin, L. C., Tseng, T. Y., Wang, S. C., & Tsai, T. H. (2007). Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 853(1–2), 183–189.CrossRefPubMed

Titel: Curcumin Nanoparticles Attenuate Neurochemical and Neurobehavioral Deficits in Experimental Model of Huntington’s Disease
verfasst von: Rajat Sandhir
Aarti Yadav
Arpit Mehrotra
Aditya Sunkaria
Amandeep Singh
Sadhna Sharma
Publikationsdatum: 01.03.2014
Verlag: Springer US
Erschienen in: NeuroMolecular Medicine / Ausgabe 1/2014
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-013-8261-y

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