646
Views
68
CrossRef citations to date
0
Altmetric
Invited Review

Antioxidant therapy in multiple sclerosis

&
Pages 13-29 | Accepted 09 Jul 2008, Published online: 17 Feb 2009

References

  • Ghafourifar, P.; Mousavizadeh, K.; Parihar, MS.; Nazarewicz, RR.; Parihar, A., and Zenebe, WJ. Mitochondria in multiple sclerosis. Front. Biosci. 2008, 13:3116–26.
  • Halliwell, B., and Gutteridge, MC. Oxygen radicals and the nervous system. Trends Neurosci. 1985, 822–29.
  • van Horssen, J.; Schreibelt, G.; Bö, L.; Montagne, L.; Drukarch, B.; van Muiswinkel, FL., and de Vries, HE. NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions. Free Radic. Biol. Med. 2006, 41:311–317.
  • Gilgun-Sherki, Y.; Melamed, E., and Offen, D. The role of oxidative stress in the pathogenesis of multiple sclerosis: The need for effective antioxidant therapy. J. Neurol. 2004, 251:261–268.
  • Schreibelt, G.; van Horssen, J.; van Rossum, S.; Dijkstra, CD.; Drukarch, B., and de Vries, HE. Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology. Brain Res. Rev. 2007, 56:322–330.
  • Trapp, BD.; Peterson, J.; Ransohoff, RM.; Rudick, R.; Mörk, S., and Bö, L. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 1998, 338:278–85.
  • Mirshafiey, A. Venom therapy in multiple sclerosis. Neuropharmacology. 2007, 53:353–61.
  • Endres, M. Statins: Potential new indications in inflammatory conditions. Atheroscler Suppl. 2006, 7:31–5.
  • Frohman, EM.; Racke, MK., and Raine, CS. Multiple sclerosis the plaque and its pathogenesis. N. Engl. J. Med. 2006, 354:942–55.
  • Mirshafiey, A. Novel promising therapeutic agents in multiple sclerosis. Recent patents on inflammation & allergy drug discovery. 2007, 1:218–224.
  • Noseworthy, JH. Progress in determining the causes and treatment of multiple sclerosis. Nature. 1999, 399:A40–7.
  • Noseworthy, JH.; Lucchinetti, C.; Rodriguez, M., and Weinshenker, BG. Multiple sclerosis. N. Engl. J. Med. 2000, 343:938–52.
  • Schrijver, HM.; Crusius, JB.; Uitdehaag, BM.; García González, MA.; Kostense, PJ.; Polman, CH., and Peña, AS. Association of interleukin- 1 beta and interleukin-1 receptor antagonist genes with diseases severity in MS. Neurology. 1999, 52:595–9.
  • Myhr, KM.; Raknes, G.; Nyland, H., and Vedeler, C. Immunoglobulin G Fc receptor (Fc gamma R) IIA and IIIB polymorphisms related to disability in MS. Neurology 1999, 52:1771–1776.
  • Evangelou, N.; Jackson, M.; Beeson, D., and Palace, J. Association of the APOE epsilon 4 allele with disease activity in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 1999, 67:203–205.
  • Sadovnick, AD.; Armstrong, H.; Rice, GP.; Bulman, D.; Hashimoto, L.; Paty, DW.; Hashimoto, SA.; Warren, S.; Hader, W.; Murray, TJ., and et al A population-based study of multiple sclerosis in twins: Update. Ann. Neurol. 1993, 33:281–285.
  • Jersild, C.; Fog, T.; Hansen, GS.; Thomsen, M.; Svejgaard, A., and Dupont, B. Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. Lancet. 1973, 2:1221–5.
  • Weinshenker, BG.; Santrach, P.; Bissonet, AS.; McDonnell, SK.; Schaid, D.; Moore, SB., and Rodriguez, M. Major histocompatibility complex class II alleles and the course and outcome of MS: a population- based study. Neurology. 1998, 51:742–747.
  • Gilgun-Sherki, Y.; Melamed, E., and Offen, D. The role of oxidative stress in the pathogenesis of multiple sclerosis: The need for effective antioxidant therapy. J. Neurol. 2004, 251:261–268.
  • Genain, CP.; Cannella, B.; Hauser, SL., and Raine, CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat. Med. 1999, 5:170–5.
  • Linington, C.; Berger, T.; Perry, L.; Weerth, S.; Hinze-Selch, D.; Zhang, Y.; Lu, HC.; Lassmann, H., and Wekerle, H. T cells specific for the myelin oligodendrocyte glycoprotein mediate an unusual autoimmune inflammatory response in the central nervous system. Eur. J. Immunol. 1993, 23:1364–72.
  • Xiao, BG., and Link, H. Antigen-specific T cells in autoimmune diseases with a focus on multiple sclerosis and experimental allergic encephalomyelitis. Cell Mol. Life Sci. 1999, 56:5–21.
  • Swanborg, RH. Animal models of human disease: experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease. Clin Immunol. Immunopathol. 1995, 77:4–13.
  • Calabrese, V.; Lodi, R.; Tonon, C.; D’Agata, V.; Sapienza, M.; Scapagnini, G.; Mangiameli, A.; Pennisi, G.; Stella, AM., and Butterfield, DA. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s ataxia. J. Neurol. Sci. 2005, 233:145–62.
  • Ruuls, SR.; Bauer, J.; Sontrop, K.; Huitinga, I.; ‘t Hart, BA., and Dijkstra, CD. Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats. J. Neuroimmunol. 1995, 56:207–217.
  • Lambeth, JD. NOX enzymes and the biology of reactive oxygen. Nat Rev. Immunol. 2004, 4:181–189.
  • Segal, BH.; Leto, LT.; Gallin, JI.; Malech, HL., and Holland, SM. Genetic biochemical and clinical features of chronic granulomatous disease. Medicine. 2000, 79:170–200.
  • Ilhan, A.; Akyol, O.; Gurel, A.; Armutcu, F.; Iraz, M., and Oztas, E. Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats. Free Radic. Biol. Med. 2004, 37:386–394.
  • Abdala-Valencia, H., and Cook-Mills, JM. VCAM-1 signals activate endothelial cell protein kinase cα via oxidation. J. Immunol. 2006, 177:6379–6387.
  • Tudor, KS.; Hess, KL., and Cook-Mills, JM. Cytokines modulate endothelial cell intracellular signal transduction required for VCAM-1-dependent lymphocyte transendothelial migration. Cytokine. 2001, 15:196–211.
  • Deem, TL., and Cook-Mills, JM. Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: Role of reactive oxygen species. Blood. 2004, 104:2385–93.
  • Hamedani, M.; Vatanpour, H.; Saadat, F.; Reza Khorramizaheh, M., and Mirshafiey, A. Bee venom, immunostimulant or immunosuppressor? Insight into the effect on matrix metalloproteinases and interferons. Immunopharmacol. Immunotoxicol. 2005, 27:671–81.
  • Matheny, HE.; Deem, TL., and Cook-Mills, JM. Lymphocyte migration through monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxidase. J. Immunol. 2000, 164:6550–655.
  • Baron, JL.; Madri, JA.; Ruddle, NH.; Hashim, G., and Janeway, CA Jr. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J. Exp. Med. 1993, 177:57–68.
  • Savina, A.; Jancic, C.; Hugues, S.; Guermonprez, P.; Vargas, P.; Moura, IC.; Lennon-Dumenil, AM.; Seabra, MC.; Raposo, G., and Amigorena, S. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell. 2006, 126:205–218.
  • Park, B.; Lee, S.; Kim, E.; Cho, K.; Riddell, SR.; Cho, S., and Ahn, K. Redox regulation facilitates optimal peptide selection by MHC class I during antigen processing. Cell. 2006, 127:369–382.
  • Lucas, M.; Rodríguez, MC.; Gata, JM.; Zayas, MD.; Solano, F., and Izquierdo, G. Regulation by interferon beta-1a of reactive oxygen metabolites production by lymphocytes and monocytes and serum sulfhydryls in relapsing multiple sclerosis patients. Neurochem. Int. 2003, 42:67–71.
  • LeVine, SM. The role of reactive oxygen species in the pathogenesis of multiple sclerosis. Med. Hypotheses. 1992, 39:271–274.
  • Lu, F.; Selak, M.; O’Connor, J.; Croul, S.; Lorenzana, C.; Butunoi, C., and Kalman, B. Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic lesions of multiple sclerosis. J. Neurol. Sci. 2000, 177:95–103.
  • Brück, W.; Sommermeier, N.; Bergmann, M.; Zettl, U.; Goebel, HH.; Kretzschmar, HA., and Lassmann, H. Macrophages in multiple sclerosis. Immunobiology. 1996, 195:588–600.
  • Nicholls, D. Mitochondrial bioenergetics, aging, and aging- related disease. Sci. Aging Knowl. Environ. 2002, pe12:
  • Beckman, KB., and Ames, BN. The free radical theory of aging matures. Physiol. Rev. 1998, 78:547–581.
  • Mirshafiey, A.; Matsuo, H.; Nakane, S.; Rehm, BH.; Koh, CS., and Miyashi, S. Novel immunosuppressive therapy by M2000 in experimental multiple sclerosis. Immunopharmacol Immunotoxicol. 2005, 27 (2):255–65.
  • Vladimirova, O.; Lu, FM.; Shawver, L., and Kalman, B. The activation of protein kinase C induces higher production of reactive oxygen species by mononuclear cells in patients with multiple sclerosis than in controls. Inflamm. Res. 1999, 48:412–6.
  • Vrabec, JP.; Lieven, CJ., and Levin, LA. Cell-type-specific opening of the retinal ganglion cell mitochondrial permeability transition pore. Invest. Ophthalmol. Vis. Sci. 2003, 44:2774–2782.
  • Banisor, I., and Kalman, B. Bcl-2 and its homologues in the brain of patients with multiple sclerosis. Mult. Scler. 2004, 10:176–181.
  • Tajouri, L.; Mellick, AS.; Ashton, KJ.; Tannenberg, AE.; Nagra, RM.; Tourtellotte, WW., and Griffiths, LR. Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis. Res. Mol. Brain Res. 2003, 119:170–183.
  • Radi, R.; Beckman, JS.; Bush, KM., and Freeman, BA. Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys. 1991, 288:481–487.
  • Beckman, JS.; Ye, YZ.; Anderson, PG.; Chen, J.; Accavitti, MA.; Tarpey, MM., and White, CR. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol. Chem. Hoppe-Seyler. 1994, 375:81–88.
  • Ischiropoulos, H.; Zhu, L.; Chen, J.; Tsai, M.; Martin, J.; Smith, C., and Beckman, JS. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch. Biochem. Biophys. 1992, 298 (4):31–437.
  • Bagasra, O.; Michaels, FH.; Zheng, YM.; Bobroski, LE.; Spitsin, SV.; Fu, ZF.; Tawadros, R., and Koprowski, H. Activation of the inducible form of nitric oxide synthase in the brains of the patients with multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A. 1995, 92:12041–5.
  • Cross, AH.; Manning, PT.; Keeling, RM.; Schmidt, RE., and Misko, TP. Peroxynitrite formation within the central nervous system in active multiple sclerosis. J. Neuroimmunol. 1998, 88:45–56.
  • Calabrese, V.; Scapagnini, G.; Ravagna, A.; Bella, R.; Butterfield, DA.; Calvani, M.; Pennisi, G., and Giuffrida Stella, AM. Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of acetylcarnitine. Neurochem. Res. 2003, 28:1321–1328.
  • Cross, AH.; Manning, PT.; Stern, MK., and Misko, TP. Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J. Neuroimmunol. 1997, 80:121–130.
  • Tran, EH.; Hardin-Pouzet, H.; Verge, G., and Owens, T. Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis. J. Neuroimmunol. 1997, 74:121–129.
  • Bates, TE.; Heales, SJ.; Davies, SE.; Boakye, P., and Clark, JB. Effects of 1-Methyl-4-phenylpyridinium on isolated rat brain mitochondria: Evidence for a primary involvement of energy depletion. J. Neurochem. 1994, 63:640–648.
  • Nathoo, N.; Barnett, GH., and Golubic, M. The eicosanoid cascade: possible role in gliomas and meningiomas. J. Clin.Pathol. 2004, 57:6–13.
  • Farooqui, AA., and Horrocks, LA. Lipid peroxides in the free radical pathophysiology of brain diseases. Cell Mol. Neurobiol. 1998, 18:599–608.
  • Kwak, MK.; Wakabayashi, N.; Itoh, K.; Motohashi, H.; Yamamoto, M., and Kensler, TW. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J. Biol. Chem. 2003, 278:8135–45.
  • Itoh, K.; Wakabayashi, N.; Katoh, Y.; Ishii, T.; O’Connor, T., and Yamamoto, M. Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells. 2003, 8:379–91.
  • McCord, JM., and Edeas, MA. SOD, oxidative stress and human pathologies: A brief history and a future vision. Biomed. Pharmacother. 2005, 59:139–42.
  • Dringen, R.; Pawlowski, PG., and Hirrlinger, J. Peroxide detoxification by brain cells. J. Neurosci. Res. 2005, 79:157–65.
  • Kim, YJ.; Ahn, JY.; Liang, P.; Ip, C.; Zhang, Y., and Park, YM. Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology. Cancer Res. 2007, 67:546–54.
  • Wagener, FA.; Volk, HD.; Willis, D.; Abraham, NG.; Soares, MP.; Adema, GJ., and Figdor, CG. Different faces of the heme–heme oxygenase system in inflammation. Pharmacol. Rev. 2003, 55:551–71.
  • Thimmulappa, RK.; Mai, KH.; Srisuma, S.; Kensler, TW.; Yamamot, M., and Biswal, S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 2002, 62:5196–203.
  • Jaiswal, AK. Regulation of genes encoding NAD(P)H:quinone oxidoreductases. Free Radic. Biol. Med. 2000, 29:254–262.
  • Ahlgren-Beckendorf, JA.; Reising, AM.; Schander, MA.; Herdler, JW., and Johnson, JA. Coordinate regulation of NAD(P.H:quinone oxidoreductase and glutathione-S-transferases in primary cultures of rat neurons and glia: Role of the antioxidant/electrophile responsive element. Glia. 1999, 25:131–142.
  • Tajouri, L.; Mellick, AS.; Ashton, KJ.; Tannenberg, AE.; Nagra, RM.; Tourtellotte, WW., and Griffiths, LR. Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis. Brain Res. Mol. Brain Res. 2003, 119:170–183.
  • Guy, J.; Qi, X., and Hauswirth, WW. Adeno-associated viral- mediated catalase expression suppresses optic neuritis in experimental allergic encephalomyelitis. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:13847–13852.
  • van-Meeteren, ME.; Teunissen, CE.; Dijkstra, CD., and van Tol, EA. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur. J. Clin. Nutr. 2005, 59:1347–1361.
  • Zachara, BA.; Gromadzinska, J.; Sklodowska, M.; Wasowicz, W.; Czernicki, J., and Maciejek, Z. Selenium status, glutathione peroxidase activity and lipid peroxides concentration in blood of multiple sclerosis patients. Acta Pharmacol. Toxicol. 1986, 59:446–449.
  • Meister, A. Glutathione-ascorbic acid antioxidant system in animals. J. Biol. Chem. 1994, 269:9397–9400.
  • Marklund, SL.; Westman, NG.; Lundgren, E., and Roos, G. Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res. 1982, 42:1955–1961.
  • Power, JH.; Shannon, JM.; Blumbergs, PC., and Gai, WP. Nonselenium glutathione peroxidase in human brain: elevated levels in Parkinson’s disease and dementia with lewy bodies. Am. J. Pathol. 2002, 161:885–894.
  • Jensen, GE., and Clausen, J. Glutathione peroxidase and reductase, glucose-6-phosphate dehydrogenase and catalase activities in multiple sclerosis. J. Neurol. Sci. 1984, 63:45–53.
  • Karg, E.; Klivényi, P.; Németh, I.; Bencsik, K.; Pintér, S., and Vécsei, L. Nonenzymatic antioxidants of blood in multiple sclerosis. J. Neurol. 1999, 246:533–539.
  • Deneke, SM.; Steiger, V., and Fanburg, BL. Effect of hyperoxia on glutathione levels and glutamic acid uptake in endothelial cells. J. Appl. Physiol. 1987, 63:1966–1971.
  • Toshniwal, PK., and Zarling, EJ. Evidence for increased lipid peroxidation in multiple sclerosis. Neurochem. Res. 1992, 17:205–207.
  • Calabrese, V.; Scapagnini, G.; Ravagna, A.; Bella, R.; Foresti, R.; Bates, TE.; Giuffrida Stella, AM., and Pennisi, G. Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels. J. Neurosci Res. 2002, 70:580–587.
  • Thorburne, SK., and Juurlink, BH. Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. J. Neurochem. 1996, 67:1014–1022.
  • Moss, DW., and Bates, TE. Activation of murine microglial cell lines by lipopolysaccharide and interferon- causes NO-mediated decreases in mitochondrial and cellular function. Eur. J. Neurosci. 2001, 13:529–538.
  • Mayer, M., and Noble, M. N-acetyl-L-cysteine is a pluripotent protector against cell death and enhancer of trophic factor-mediated cell survival in vitro. Proc. Natl. Acad.Sci. U.S.A. 1994, 91:7496–7500.
  • Bizzozero, OA.; Dejesus, G.; Callahan, K., and Pastuszyn, A. Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis. J. Neurosci. Res. 2005, 81:687–695.
  • Levine, SM., and Chakrabarty, A. The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis. Ann. N.Y. Acad. Sci. 2004, 1012:252–266.
  • Andrews, HE.; Nichols, PP.; Bates, D., and Turnbull, DM. Mitochondrial dysfunction plays a key role in progressive axonal loss in multiple sclerosis. Med. Hypotheses. 2005, 64:669–677.
  • Butterfield, DA., and Lauderback, CM. Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic. Biol. Med. 2002, 32:1050–1060.
  • Bizzozero, OA.; Ziegler, JL.; De Jesus, G., and Bolognani, F. Acute depletion of reduced glutathione causes extensive carbonylation of rat brain proteins. J. Neurosci. Res. 2006, 83:656–667.
  • Hofmann, B.; Hecht, HJ., and Flohe, L. Peroxiredoxins. Biol. Chem. 2002, 383:347–364.
  • McCord, JM. Iron- and manganese-containing superoxide dismutases: structure, distribution, and evolutionary relationships. Adv. Exp. Med. Biol. 1976, 74:540–550.
  • Marklund, SL.; Westman, NG.; Lundgren, E., and Roos, G. Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res. 1982, 42:1955–1961.
  • Orr, WC.; Mockett, RJ.; Benes, JJ., and Sohal, RS. Effects of overexpression of copper–zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster. J. Biol. Chem. 2003, 278:26418–26422.
  • Afonso, V.; Champy, R.; Mitrovic, D.; Collin, P., and Lomri, A. Reactive oxygen species and superoxide dismutases: Role in joint diseases. Joint Bone Spine. 2007, 74:324–329.
  • Morten, KJ.; Ackrell, BA., and Melov, S. Mitochondrial reactive oxygen species in mice lacking superoxide dismutase 2: Attenuation via antioxidant treatment. J. Biol. Chem. 2006, 281:3354–3359.
  • Kiningham, KK.; Xu, Y.; Daosukho, C.; Popova, B., and St Clair, DK. Nuclear factor kappaB-dependent mechanisms coordinate the synergistic effect of PMA and cytokines on the induction of superoxide dismutase 2.. Biochem. J. 2001, 353:147–156.
  • Fattman, CL.; Schaefer, LM., and Oury, TD. Extracellular superoxide dismutase in biology and medicine. Free Radic Biol. Med. 2003, 35:236–256.
  • Enghild, JJ.; Thogersen, IB.; Oury, TD.; Valnickova, Z.; Hojrup, P., and Crapo, JD. The heparin-binding domain of extracellular superoxide dismutase is proteolytically processed intracellularly during biosynthesis. J. Biol. Chem. 1999, 274:14818–14822.
  • Ceballos, I.; Javoy-Agid, F.; Delacourte, A.; Defossez, A.; Lafon, M.; Hirsch, E.; Nicole, A.; Sinet, PM., and Agid, Y. Neuronal localization of copper–zinc superoxide dismutase protein and mRNA within the human hippocampus from control and Alzheimer’s disease brains. Free Radic. Res. Commun. 1991, 2:571–80.
  • Zagórski, T.; Dudek, I.; Berkan, L.; Mazurek, M.; Kedziora, J., and Chmielewski, H. [Superoxide dismutase (SOD–1) activity in erythrocytes of patients with multiple sclerosis].. Neurol. Neurochir. Pol. 1991, 25:725–30.
  • Qi, X.; Guy, J.; Nick, H.; Valentine, J., and Rao, N. Increase of manganese superoxide dismutase, but not of Cu/Zn–SOD, in experimental optic neuritis. Invest. Ophthalmol. Vis. Sci. 1997, 38:1203–1212.
  • Peng, J.; Stevenson, FF.; Doctrow, SR., and Andersen, JK. Superoxide dismutase/catalase mimetics are neuroprotective against selective paraquat-mediated dopaminergic neuron death in the substantial nigra: implications for Parkinson disease. J. Biol. Chem. 2005, 280:29194–29198.
  • Sharpe, MA.; Ollosson, R.; Stewart, VC., and Clark, JB. Oxidation of nitric oxide by oxomanganese–salen complexes: A new mechanism for cellular protection by superoxide dismutase/catalase mimetics. Biochem. J. 2002, 366:97–107.
  • Bruce, AJ.; Malfroy, B., and Baudry, M. Beta-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:2312–6.
  • Pong, K.; Doctrow, SR., and Baudry, M. Prevention of 1- methyl-4-phenylpyridinium- and 6-hydroxydopamine-induced nitration of tyrosine hydroxylase and neurotoxicity by EUK-134, a superoxide dismutase and catalase mimetic, in cultured dopaminergic neurons. Brain Res. 2000, 881:182–9.
  • Baker, K.; Marcus, CB.; Huffman, K.; Kruk, H.; Malfroy, B., and Doctrow, SR. Synthetic combined superoxide dismutase/catalase mimics are protective as a delayed treatment in a rat stroke mode: A key role for reactive oxygen species in ischemic brain injury. J. Pharmacol. Exp. Ther. 1998, 284:215–221.
  • Jung, C.; Rong, Y.; Doctrow, S.; Baudry, M.; Malfroy, B., and Xu, Z. Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model. Neurosci. Lett. 2001, 304:157–160.
  • Malfroy, B.; Doctrow, SR.; Orr, PL.; Tocco, G.; Fedoseyeva, EV., and Benichou, G. Prevention and suppression of autoimmune encephalomyelitis by EUK-8, a synthetic catalytic scavenger of oxygen reactive metabolites. Cell. Immunol. 1997, 177:62–68.
  • Osman, R., and Basch, H. On the mechanism of action of superoxide-dismutase ± a theoretical-study. J. Am. Chem. Soc. 1984, 106:5710–5714.
  • Aebi, H. Catalase in vitro. Methods Enzymol. 1984, 105:121–126.
  • Baud, O.; Greene, AE.; Li, J.; Wang, H.; Volpe, JJ., and Rosenberg, PA. Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J. Neurosc. 2004, 24:1531–1540.
  • Kim, Y S., and Kim, S U. Oligodendroglial cell death induced by oxygen radicals and its protection by catalase. J. Neurosci Res. 1991, 29:100–106.
  • Guy, J.; McGorray, S.; Fitzsimmons, J.; Beck, B.; Mancuso, A.; Rao, N A., and Hamed, L. Reversals of blood-brain barrier disruption by catalase: A serial magnetic resonance imaging study of experimental optic neuritis. Invest. Ophthalmol. Vis. Sci. 1994, 35:3456–3465.
  • Guy, J.; Ellis, EA.; Hope, GM., and Rao, NA. Antioxidant enzyme suppression of demyelination in experimental optic neuritis. Curr. Eye Res. 1989, 8:467–477.
  • Qi, X.; Hauswirth, WW., and Guy, J. Dual gene therapy with extracellular superoxide dismutase and catalase attenuates experimental optic neuritis. Mol Vis. 2007, 13:1–11.
  • Van der Goes, A.; Wouters, D.; Van Der Pol, SM.; Huizinga, R.; Ronken, E.; Adamson, P.; Greenwood, J.; Dijkstra, CD., and De Vries, HE. Reactive oxygen species enhance the migration of monocytes across the blood-brain barrier in vitro. FASEB J. 2001, 15:1852–1854.
  • Smith, KJ.; Kapoor, R., and Felts, PA. Demyelination: The role of reactive oxygen and nitrogen species. Brain Pathol. 1999, 9:69–92.
  • Siegel, D., and Ross, D. Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues, Free Radic. Biol. Med. 2000, 29:246–253.
  • Murphy, TH.; Yu, J.; Ng, R.; Johnson, DA.; Shen, H.; Honey, CR., and Johnson, JA. Preferential expression of antioxidant response element mediated gene expression in astrocytes. J. Neurochem. 2001, 76:1670–1678.
  • Wierinckx, A.; Brevé, J.; Mercier, D.; Schultzberg, M.; Drukarch, B., and Van Dam, AM. Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J. Neuroimmunol. 2005, 166:132–43.
  • Yeldandi, AV.; Yeldandi, V.; Kumar, S.; Murthy, CV.; Wang, XD.; Alvares, K.; Rao, MS., and Reddy, JK. Molecular evolution of the urate oxidase-encoding gene in hominid primates: nonsense mutations. Gene. 1991, 109:281–284.
  • Mousavizadeh, K.; Dehpour, AR.; Minagar, A., and Ghafourifar, P. Uric acid: a novel treatment strategy for multiple sclerosis. Trends Pharmacol. Sci. 2003, 24:563–564.
  • Guerrero, AL.; Martín-Polo, J.; Laherrán, E.; Gutiérrez, F.; Iglesias, F.; Tejero, MA.; Rodríguez-Gallego, M., and Alcázar, C. Variation of serum uric acid levels in multiple sclerosis during relapses and immunomodulatory treatment. Eur. J. Neurol. 2008, 15:394–397.
  • Kean, RB.; Spitsin, SV.; Mikheeva, T.; Scott, GS., and Hooper, DC. The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. J. Immunol. 2000, 165:6511–6518.
  • Hediger, MA. Gateway to a long life?. Nature. 2002, 417:393–395.
  • Rentzos, M.; Nikolaou, C.; Anagnostouli, M.; Rombos, A.; Tsakanikas, K.; Economou, M.; Dimitrakopoulos, A.; Karouli, M., and Vassilopoulos, D. Serum uric acid and multiple sclerosis. Neurol. Sci. 2002, 23:183–188.
  • Hooper, DC.; Spitsin, S.; Kean, RB.; Champion, JM.; Dickson, GM.; Chaudhry, I., and Koprowski, H. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:675–680.
  • Saadat, F.; Cuzzocrea, S.; Di Paolo, R.; Pezeshki, M.; Khorramizadeh, MR.; Sedaghat, M.; Razavi, A., and Mirshafiey, A. Effect of pyrimethamine in experimental rheumatoid arthritis. Med. Sci. Monit. 2005, 11:293–299.
  • Saleh, D.; Ernst, P.; Lim, S.; Barnes, PJ., and Giaid, A. Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: Effect of inhaled glucocorticoid. FASEB J. 1998, 12:929–937.
  • Szabó, C.; Salzman, AL., and Ischiropoulos, H. Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo. FEBS Lett. 1995, 363:235–238.
  • Rachmilewitz, D.; Stamler, JS.; Karmeli, F.; Mullins, ME.; Singel, DJ.; Loscalzo, J.; Xavier, RJ., and Podolsky, DK. Peroxynitrite-induced rat colitis:A new model of colonic inflammation. Gastroenterology. 1993, 105:1681–1688.
  • Oury, TD.; Piantadosi, CA., and Crapo, JD. Cold-induced brain edema in mice. Involvement of extracellular superoxide dismutase and nitric oxide. J. Biol. Chem. 1993, 268:15394–15398.
  • Smith, MA.; Richey Harris, PL.; Sayre, LM.; Beckman, JS., and Perry, G. Widespread peroxynitrite-mediated damage in Alzheimer’s disease. J. Neurosci. 1997, 17:2653–2657.
  • Good, PF.; Hsu, A.; Werner, P.; Perl, DP., and Olanow, CW. Protein nitration in Parkinson’s disease. J. Neuropathol Exp. Neurol. 1998, 57:338–342.
  • Crow, JP.; Sampson, JB.; Zhuang, Y.; Thompson, JA., and Beckman, JS. Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J. Neurochem. 1997, 69:1936–1944.
  • Pacher, P., and Szabo, C. Role of the peroxynitrite-poly (ADP-ribose) polymerase pathway in human disease. Am. J. Pathol 2008, 173:2–13.
  • Roggensack, AM.; Zhang, Y., and Davidge, ST. Evidence for peroxynitrite formation in the vasculature of women with preeclampsia. Hypertension. 1999, 33:83–89.
  • Hensley, K.; Tabatabaie, T.; Stewart, CA.; Pye, Q., and Floyd, RA. Nitric oxide and derived species as toxic agents in stroke, AIDS, dementia, and chronic neurodegenerative disorders. Chem Res. Toxicol. 1997, 10:527–532.
  • Toncev, G.; Milicic, B.; Toncev, S., and Samardzic, G. Serum uric acid levels in multiple sclerosis patients correlate with activity of disease and blood-brain barrier dysfunction. Eur J. Neurol. 2002, 9:221–226.
  • Spitsin, SV.; Scott, GS.; Kean, RB.; Mikheeva, T., and Hooper, DC. Protection of myelin basic protein immunized mice from free-radical mediated inflammatory cell invasion of the central nervous system by the natural peroxynitrite scavenger uric acid. Neurosci Lett. 2000, 292:137–141.
  • Hooper, DC.; Spitsin, S.; Kean, RB.; Champion, JM.; Dickson, GM.; Chaudhry, I., and Koprowski, H. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci. USA. 1998, 95:675–680.
  • Kanabrocki, EL.; Third, JL.; Ryan, MD.; Nemchausky, BA.; Shirazi, P.; Scheving, LE.; McCormick, JB.; Hermida, RC.; Bremner, WF.; Hoppensteadt, DA.; Fareed, J., and Olwin, JH. Circadian relationship of serum uric acid and nitric oxide. J. Am. Med. Assoc. 2000, 283:2240–2241.
  • Marracci, GH.; McKeon, GP.; Marquardt, WE.; Winter, RW.; Riscoe, MK., and Bourdette, DN. αlipoic acid inhibits human T-cell migration: Implications for multiple sclerosis. J. Neurosci. Res. 2004, 78:362–370.
  • Schreibelt, G.; Musters, RJ.; Reijerkerk, A.; de Groot, LR.; van der Pol, SM.; Hendrikx, EM.; Döpp, ED.; Dijkstra, CD.; Drukarch, B., and de Vries, HE. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J. Immunol. 2006, 177:2630–2637.
  • Cho, KJ.; Moini, H.; Shon, HK.; Chung, AS., and Packer, L. [alpha]-Lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3–L1 adipocytes. Biochem. Pharmacol. 2003, 66:849–58.
  • Hooper, DC.; Bagasra, O.; Marini, JC.; Zborek, A.; Ohnish,i, ST.; Kean, R.; Champion, JM.; Sarker, AB.; Bobroski, L.; Farber, JL.; Akaike, T.; Maeda, H., and Koprowski, H. Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: Implications for the treatment of multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A. 1997, 94:2528–2533.
  • Schillace, RV.; Pisenti, N.; Pattamanuch, N.; Galligan, S.; Marracci, GH.; Bourdette, DN., and Carr, DW. Lipoic acid stimulates cAMP production in T lymphocytes and NK cells. Biochem. Biophys Res. Commun. 2007, 354:259–264.
  • Yadav, V.; Marracc, G.; Lovera, J.; Woodward, W.; Bogardus, K.; Marquardt, W.; Shinto, L.; Morris, C., and Bourdette, D. Lipoic acid in multiple sclerosis: A pilot study. Mult. Scler. 2005, 11:159–165.
  • Frei, B., and Higdon, JV. Antioxidant activity of tea polyphenols in vivo: Evidence from animal studies. J. Nutr. 2003, 133:3275–3284.
  • Bowie, A., and O’Neill, LA. Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem. Pharmacol. 2000, 59:13–23.
  • Marracci, GH.; Marquardt, WE.; Strehlow, A.; McKeon, GP.; Gross, J.; Buck, DC.; Kozell, LB., and Bourdette, DN. Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56Lck. Biochem. Biophys. Res. Commun. 2006, 344:963–971.
  • Liu, Y.; Zhu, B.; Wang, X.; Luo, L.; Li, P.; Paty, DW., and Cynader, MS. Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: Implications for the role of oxidative stress in the development of multiple sclerosis. J. Neuroimmunol. 2003, 139:27–35.
  • Stocker, R.; Yamamoto, Y.; McDonagh, AF.; Glazer, AN., and Ames, BN. Bilirubin is an antioxidant of possible physiological importance. Science. 1987, 235:1043–1046.
  • Liu, Y.; Liu, J.; Tetzlaff, W.; Paty, DW., and Cynader, MS. Biliverdin reductase, a major physiologic cytoprotectant, suppresses experimental autoimmune encephalomyelitis. Free Radic. Biol. Med. 2006, 40:960–967.
  • van Meeteren, M.E.; Teunissen, C.E.; Dijkstra, C.D., and van Tol, E.A.F. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur. J. Clin. Nutr. 2005, 59:1347–1361.
  • Simopoulos, AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J. Am. Coll. Nutr. 2002, 21:495–505.
  • Weinstock-Guttman, B.; Baier, M.; Park, Y.; Feichter, J.; Lee-Kwen, P.; Gallagher, E.; Venkatraman, J.; Meksawan, K.; Deinehert, S.; Pendergast, D.; Awad, AB.; Ramanathan, M.; Munschauer, F., and Rudick, R. Low fat dietary intervention with ω-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot. Essent. Fatty Acids. 2005, 73:397–404.
  • Holian, O., and Nelson, R. Action of long-chain fatty acids on protein kinase C activity: Comparison of omega-6 and omega-3 fatty acids. Anticancer Res. 1992, 12:975–980.
  • Calder, PC. Fat chance of immunomodulation. Trends Immunol. Today. 1998, 6:244–247.
  • Mazza, M.; Pomponi, M.; Janiri, L.; Bria, P., and Mazza, S. Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases, An overview. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2007, 31:12–26.
  • Aupperle, RL.; Denney, DR.; Lynch, SG.; Carlson, SE., and Sullivan, DK. Omega-3 fatty acids and multiple sclerosis: Relationship to depression. J. Behav. Med. 2008, 31:127–135.
  • Lukiw, WJ.; Cui, JG.; Marcheselli, VL.; Bodke, r M.; Botkjaer, A.; Gotlinger, K.; Serhan, CN., and Bazan, NG. Role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J. Clin. Invest. 2005, 115:2774–2783.
  • Rossary, A.; Arab, K., and Steghens, JP. Polyunsaturated fatty acids modulate NOX 4 anion superoxide production in human fibroblasts. Biochem. J. 2007, 406:77–83.
  • Weinstock-Guttman, B.; Baier, M.; Park, Y.; Feichter, J.; Lee-Kwen, P.; Gallagher, E.; Venkatraman, J.; Meksawan, K.; Deinehert, S.; Pendergast, D.; Awad, AB.; Ramanathan, M.; Munschauer, F., and Rudick, R. Low fat dietary intervention with ω-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot. Essen. Fatty Acids. 2005, 73:397–404.
  • Stepien, K.; Tomaszewski, M., and Czuczwar, SJ. Neuroprotective properties of statins. Pharmacol. Rep. 2005, 57:561–9.
  • Youssef, S.; Stüve, O.; Patarroyo, JC.; Ruiz, PJ.; Radosevich, JL.; Hur, EM.; Bravo, M.; Mitchell, DJ.; Sobel, RA.; Steinman, L., and Zamvil, SS. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002, 420:78–84.
  • Aktas, O.; Waiczies, S.; Smorodchenko, A.; Dorr, J.; Seeger, B.; Prozorovski, T.; Sallach, S.; Endres, M.; Brocke, S.; Nitsch, R., and Zipp, F. Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J. Exp. Med. 2003, 197:725–733.
  • Pannu, R., and Singh, I. Pharmacological strategies for the regulation of inducible nitric oxide synthase: Neurodegenerative versus neuroprotective mechanisms. Neurochem. Int. 2006, 49:170–182.
  • Endres, M. Statins: Potential new indications in inflammatory conditions. Atheroscler Suppl. 2006, 7:31–35.
  • Menge, T.; Hartung, HP., and Stüve, O. Statins—A cure-all for the brain?. Nat. Rev. 2005, 6:325–351.
  • Galea, E.; Reis, DJ.; Xu, H., and Feinstein, DL. Transient expression of calcium-independent nitric oxide synthase in blood vessels during brain development. FASEB J. 1995, 9:1632–1637.
  • Pahan, K.; Namboodiri, AM.; Sheikh, FG.; Smith, BT., and Singh, I. Increasing cAMP attenuates induction of inducible nitric-oxide synthase in rat primary astrocytes. J. Biol. Chem. 1997, 272:7786–7791.
  • Besler, HT.; Comoglu, S., and Okçu, Z. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutr. Neurosci. 2002, 5:215–20.
  • Jiménez-Jiménez, FJ.; de Bustos, F.; Molina, JA.; de Andrés, C.; Gasalla, T.; Ortí-Pareja, M.; Zurdo, M.; Porta, J.; Castellano-Millán, F.; Arenas, J., and Enríquez de Salamanca, R. Cerebrospinal fluid levels of alpha-tocopherol in patients with multiple sclerosis. Neurosci. Lett. 1998, 249:65–67.
  • Jiménez-Jiménez, FJ.; de Bustos, F.; Molina, JA.; Benito-León, J.; Tallón-Barranco, A.; Gasalla, T.; Ortí-Pareja, M.; Guillamón, F.; Rubio, JC.; Arenas, J., and Enríquez-de-Salamanca, R. Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer’s disease. J. Neural. Transm. 1997, 104:703–710.
  • Guthikonda, P.; Baker, J., and Mattson, DH. Interferon-beta-1-b (IFN-B) decreases induced nitric oxide (NO) production by a human astrocytoma cell line. J. Neuroimmunol. 1998, 82:133–139.
  • Thurnham, DI.; Davies, JA.; Crump, BJ.; Situnayake, RD., and Davis, M. The use of different lipids to express serum tocopherol:lipid ratios for the measurement of vitamin E status. Ann. Clin. Biochem. 1986, 23:514–520.
  • Butterfield, DA.; Castegna, A.; Drake, J.; Scapagnini, G., and Calabrese, V. Vitamin E and neurodegenerative disorders associated with oxidative stress. Nutr. Neurosci. 2002, 5:229–239.
  • de Andrés, C., and Lledó, A. Fatty diet and multiple sclerosis. Rev. Neurol. 1997, 25:2032–2035.
  • Chun, TY.; Carman, JA., and Hayes, CE. Retinoid repletion of vitamin A-deficient mice restores IgG responses. J. Nutr. 1992, 122:1062–1069.
  • Qu, ZX.; Dayal, A.; Jensen, MA., and Arnason, BG. All-trans retinoic acid potentiates the ability of interferon beta-1b to augment suppressor cell function in multiple sclerosis. Arch. Neurol. 1998, 55:315–321.
  • Desvergne, B., and Wahli, W. Peroxisome proliferator-activated receptors: Nuclear control of metabolism. Endocr. Rev. 1999, 20:649–688.
  • Lee, C-H.; Olson, P., and Evans, RM. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology. 2003, 144:2201–2207.
  • Xu, J.; Storer, PD.; Chavis, JA.; Racke, MK., and Drew, PD. Agonists for the peroxisome proliferator-activated receptor-α and the retinoid X receptor inhibit inflammatory responses of microglia. J. Neurosci. Res. 2005, 81:403–411.
  • Pedersen, LB.; Nashold, FE.; Spach, KM., and Hayes, CE. 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking. J. Neurosci. Res. 2007, 85:2480–2490.
  • Spach, KM., and Hayes, CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J. Immunol. 2005, 175:4119–4126.
  • Hayes, CE.; Nashold, FE.; Spach, KM., and Pedersen, LB. The immunological functions of the vitamin D endocrine system. Cell Mol. Biol. (Noisy-le-grand). 2003, 49:277–300.
  • Lambert, JD.; Sang, S., and Yang, CS. Biotransformation of green tea polyphenols and the biological activities of those metabolites. Mol Pharm. 2007, 4:819–25.
  • Révész, K.; Tüttô, A., and Konta, L. Effect of green tea flavonols on the function of the endoplasmic reticulum. Orv Hetil. 2007, 148:1903–7.
  • Aktas, O.; Prozorovski, T.; Smorodchenko, A.; Savaskan, NE.; Lauster, R.; Kloetzel, PM.; Infante-Duarte, C.; Brocke, S., and Zipp, F. Green Tea Epigallocatechin-3-Gallate mediates t cellular nf-b inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J. Immunol. 2004, 173:5794–5800.
  • Haqqi, TM.; Anthony, DD.; Gupta, S.; Ahmad, N.; Lee, MS.; Kumar, GK., and Mukhtar, H. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:4524–9.
  • Hinz, M.; Krappmann, D.; Eichten, A.; Heder, A.; Scheidereit, C., and Strauss, M. NF-B function in growth control: Regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol. Cell Biol. 1999, 19:2690–8.
  • Jiang, RW.; Lau, KM.; Hon, PM.; Mak, TC.; Woo, KS., and Fung, KP. Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza. Curr. Med. Chem. 2005, 12:237–46.
  • Yang, JQ.; Zho,u, QX.; Liu, BZ., and He, BC. Protection of mouse brain from aluminum-induced damage by caffeic acid. CNS Neurosci. Ther. 2008, 14:10–6.
  • Sud’ina, GF.; Mirzoeva, OK.; Pushkareva, MA.; Korshunova, GA.; Sumbatyan, NV., and Varfolomeev, SD. Caffeic acid phenethyl ester as a lipooxygenase inhibitor with antioxidant properties. FEBS Lett. 1993, 329:21–24.
  • Ilhan, A.; Akyol, O.; lA, Gure.; Armutcu, F.; Iraz, M., and Oztas, E. Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats. Free Radic. Biol. Med. 2004, 37:386–394.
  • Song, YS.; Park, EH.; Hur, GM.; Ryu, YS.; Lee, YS.; Lee, JY.; Kim, YM., and Jin, C. Caffeic acid phenethyl ester inhibits nitric oxide synthase gene expression and enzyme activity. Cancer Lett. 2002, 175:53–61.
  • Natarajan, K.; Singh, S.; Burke, TR.Jr.;; Grunberger, D., and Aggarwal, BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NFkappa B.. Proc. Natl. Acad. Sci. U.S.A. 1996, 93:9090–9095.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.