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Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

Douglas B Kell

BMC Medical Genomics · 2009 · Review

Abstract

Background. The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation.

Review. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, since in some circumstances (especially the presence of poorly liganded iron) molecules that are nominally antioxidants can actually act as pro-oxidants. The reduction of redox stress thus requires suitable levels of both antioxidants and effective iron chelators. Some polyphenolic antioxidants may serve both roles. Understanding the exact speciation and liganding of iron in all its states is thus crucial to separating its various pro- and anti-inflammatory activities. Redox stress, innate immunity and pro- (and some anti-)inflammatory cytokines are linked in particular via signalling pathways involving NF-kappaB and p38, with the oxidative roles of iron here seemingly involved upstream of the IkappaB kinase (IKK) reaction. In a number of cases it is possible to identify mechanisms by which ROSs and poorly liganded iron act synergistically and autocatalytically, leading to 'runaway' reactions that are hard to control unless one tackles multiple sites of action simultaneously. Some molecules such as statins and erythropoietin, not traditionally associated with anti-inflammatory activity, do indeed have 'pleiotropic' anti-inflammatory effects that may be of benefit here.

Conclusion. Overall we argue, by synthesising a widely dispersed literature, that the role of poorly liganded iron has been rather underappreciated in the past, and that in combination with peroxide and superoxide its activity underpins the behaviour of a great many physiological processes that degrade over time. Understanding these requires an integrative, systems-level approach that may lead to novel therapeutic targets.

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240.
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Wessling-Resnick M. Iron Imports. III. Transfer of iron from the mucosa into circulation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006;290:G1-G6.
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Moriya M, Linder MC. Vesicular transport and apotransferrin in intestinal iron absorption, as shown in the Caco-2 cell model. Amer J Physiol. 2006;290:G301-G309.
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Petrat F, de Groot H, Sustmann R, Rauen U. The chelatable iron pool in living cells: A methodically defined quantity. Biological Chemistry. 2002;383:489-502.
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Ganz T. Cellular iron: ferroportin is the only way out. Cell Metab. 2005;1:155-7.
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Foresti R, Green CJ, Motterlini R. Generation of bile pigments by haem oxygenase: a refined cellular strategy in response to stressful insults. Biochem Soc Symp. 2004;71:177-192.
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Poon HF, Calabrese V, Scapagnini G, Butterfield DA. Free radicals: key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol A Biol Sci Med Sci. 2004;59:478-93.
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Lee DW, Andersen JK. Role of HIF-1 in iron regulation: potential therapeutic strategy for neurodegenerative disorders. Curr Mol Med. 2006;6:883-893.
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286.
Rouault TA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nature Chem Biol. 2006;2:406-414.
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Wallander ML, Leibold EA, Eisenstein RS. Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim Biophys Acta. 2006;1763:668-689.
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Lee K, Roth RA, LaPres JJ. Hypoxia, drug therapy and toxicity. Pharmacology & Therapeutics. 2007;113:229-246.
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289.
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Fleming RE, Sly WS. Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Nal Acad Sci. 2001;98:8160-8162.
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Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci. 2001;98:8780-8785.
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Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood. 2002;100:3776-81.
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Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DHG, Subramaniam VN, Powell LW, Anderson GJ, Ramm GA. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet. 2003;361:669-673.
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Nicolas G, Viatte L, Lou DQ, Bennoun M, Beaumont C, Kahn A, Andrews NC, Vaulont S. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nature Genetics. 2003;34:97-101.
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Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, Loukopoulos D, Camaschella C. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nature Genetics. 2003;33:21-22.
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Deicher R, Horl WH. Hepcidin: a molecular link between inflammation and anaemia. Nephrol Dial Transplant. 2004;19:521-4.
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Leong WI, Lönnerdal B. Hepcidin, the recently identified peptide that appears to regulate iron absorption. J Nutr. 2004;134:1-4.
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298.
Robson KJ. Hepcidin and its role in iron absorption. Gut. 2004;53:617-9.
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299.
Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood. 2005;106:3710-7.
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301.
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Roy CN, Andrews NC. Anemia of inflammation: the hepcidin link. Curr Opin Hematol. 2005;12:107-11.
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303.
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305.
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306.
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Harrison-Findik DD, Schafer D, Klein E, Timchenko NA, Kulaksiz H, Clemens D, Fein E, Andriopoulos B, Pantopoulos K, Gollan J. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem. 2006;281:22974-22982.
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309.
Mena NP, Esparza AL, Núñez MT. Regulation of transepithelial transport of iron by hepcidin. Biol Res. 2006;39:191-193.
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310.
Mok H, Mlodnicka AE, Hentze MW, Muckenthaler M, Schumacher A. The molecular circuitry regulating the switch between iron deficiency and overload in mice. J Biol Chem. 2006;281:7946-51.
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311.
Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annual Review of Nutrition. 2006;26:323-342.
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312.
Atanasiu V, Manolescu B, Stoian I. Hepcidin – central regulator of iron metabolism. European Journal of Haematology. 2007;78:1-10.
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313.
Malyszko J, Mysliwiec M. Hepcidin in anemia and inflammation in chronic kidney disease. Kidney & Blood Pressure Research. 2007;30:15-30.
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314.
Oates PS, Ahmed U. Molecular regulation of hepatic expression of iron regulatory hormone hepcidin. J Gastroenterol Hepatol. 2007;22:1378-87.
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Barisani D, Pelucchi S, Mariani R, Galimberti S, Trombini P, Fumagalli D, Meneveri R, Nemeth E, Ganz T, Piperno A. Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload. J Hepatol. 2008;49:123-33.
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316.
Camaschella C, Silvestri L. New and old players in the hepcidin pathway. Haematologica. 2008;93:1441-4.
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317.
De Domenico I, Nemeth E, Nelson JM, Phillips JD, Ajioka RS, Kay MS, Kushner JP, Ganz T, Ward DM, Kaplan J. The hepcidin-binding site on ferroportin is evolutionarily conserved. Cell Metab. 2008;8:146-56.
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318.
Farnaud S, Rapisarda C, Bui T, Drake A, Cammack R, Evans RW. Identification of an iron-hepcidin complex. Biochem J. 2008;413:553-7.
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Kartikasari AE, Roelofs R, Schaeps RM, Kemna EH, Peters WH, Swinkels DW, Tjalsma H. Secretion of bioactive hepcidin-25 by liver cells correlates with its gene transcription and points towards synergism between iron and inflammation signaling pathways. Biochim Biophys Acta. 2008;1784:2029-37.
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320.
Muckenthaler MU, Galy B, Hentze MW. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr. 2008;28:197-213.
Not in our library10.1146/annurev.nutr.28.061807.155521
321.
Nemeth E. Iron regulation and erythropoiesis. Curr Opin Hematol. 2008;15:169-75.
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322.
Nishina S, Hino K, Korenaga M, Vecchi C, Pietrangelo A, Mizukami Y, Furutani T, Sakai A, Okuda M, Hidaka I, Okita K, Sakaida I. Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology. 2008;134:226-38.
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Peeling P, Dawson B, Goodman C, Landers G, Trinder D. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol. 2008;103:381-91.
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324.
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325.
Swinkels DW, Wetzels JF. Hepcidin: a new tool in the management of anaemia in patients with chronic kidney disease? Nephrol Dial Transplant. 2008;23:2450-3.
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Toblli JE, Cao G, Rivas C, Kulaksiz H. Heart and iron deficiency anaemia in rats with renal insufficiency: The role of hepcidin. Nephrology (Carlton). 2008;13:636-645.
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Trinder D, Ayonrinde OT, Olynyk JK. HCV, iron, and oxidative stress: the new choreography of hepcidin. Gastroenterology. 2008;134:348-51.
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328.
Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M. Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci USA. 2005;102:1324-8.
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329.
Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090-2093.
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330.
Delaby C, Pilard N, Goncalves AS, Beaumont C, Canonne-Hergaux F. Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin. Blood. 2005;106:3979-84.
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331.
Ganz T. Hepcidin – a regulator of intestinal iron absorption and iron recycling by macrophages. Best Practice & Research Clinical Haematology. 2005;18:171-182.
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332.
Papanikolaou G, Tzilianos M, Christakis JI, Bogdanos D, Tsimirika K, MacFarlane J, Goldberg YP, Sakellaropoulos N, Ganz T, Nemeth E. Hepcidin in iron overload disorders. Blood. 2005;105:4103-4105.
Not in our library10.1182/blood-2004-12-4844
333.
Lesbordes-Brion JC, Viatte L, Bennoun M, Lou DQ, Ramey G, Houbron C, Hamard G, Kahn A, Vaulont S. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood. 2006;108:1402-1405.
Not in our library10.1182/blood-2006-02-003376
334.
Anderson GJ, Frazer DM. Iron metabolism meets signal transduction. Nature Genetics. 2006;38:503-504.
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335.
Kulaksiz H, Gehrke SG, Janetzko A, Rost D, Bruckner T, Kallinowski B, Stremmel W. Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia. Gut. 2004;53:735-743.
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336.
Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D, Janetzko A, Cetin Y, Stremmel W. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. Journal of Endocrinology. 2005;184:361-370.
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337.
Tiker F, Celik B, Tarcan A, Kilicdag H, Ozbek N, Gurakan B. Serum pro-hepcidin levels and relationships with iron parameters in healthy preterm and term newborns. Pediatr Hematol Oncol. 2006;23:293-297.
Not in our library10.1080/08880010600629213
338.
Roe MA, Spinks C, Heath ALM, Harvey LJ, Foxall R, Wimperis J, Wolf C, Fairweather-Tait SJ. Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying. HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women. Br J Nutr. 2007;97:544-549.
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339.
Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110:1037-1044.
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340.
Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006;108:3730-5.
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341.
Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101:2461-2463.
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342.
Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271-1276.
Not in our library10.1172/jci20945
343.
Kemna E, Pickkers P, Nemeth E, Hoeven H van der, Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005;106:1864-1866.
Not in our library10.1182/blood-2005-03-1159
344.
Fleming RE. Iron and inflammation: cross-talk between pathways regulating hepcidin. J Mol Med. 2008;86:491-4.
Not in our library10.1007/s00109-008-0349-8
345.
Malyszko J, Malyszko JS, Pawlak K, Drozdowska-Rams L, Brzosko S, Mysliwiec M. Hepcidin is linked to anemia and inflammation in peritoneal dialysis patients. Perit Dial Int. 2008;28:418-21.
Not in our library
346.
Wang RH, Li CL, Xu XL, Zheng Y, Xiao CY, Zerfas P, Cooperman S, Eckhaus M, Rouault T, Mishra L, Deng CX. A role of SMAD4 in iron metabolism through the positive regulation of hepicidin expression. Cell Metabolism. 2005;2:399-409.
Not in our library10.1016/j.cmet.2005.10.010
347.
Falzacappa MVV, Spasic MV, Kessler R, Stolte J, Hentze MW, Muckenthaler MU. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood. 2007;109:353-358.
Not in our library10.1182/blood-2006-07-033969
348.
Pietrangelo A, Dierssen U, Valli L, Garuti C, Rump A, Corradini E, Ernst M, Klein C, Trautwein C. STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo. Gastroenterol. 2007;132:294-300.
Not in our library10.1053/j.gastro.2006.10.018
349.
Choi SO, Cho YS, Kim HL, Park JW. ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBP alpha and STAT-3. Biochem Biophys Res Comm. 2007;356:312-317.
Not in our library10.1016/j.bbrc.2007.02.137
350.
Flanagan JM, Truksa J, Peng HF, Lee P, Beutler E. In vivo imaging of hepcidin promoter stimulation by iron and inflammation. Blood Cells Mols Dis. 2007;38:253-257.
Not in our library10.1016/j.bcmd.2007.01.004
351.
Détivaud L, Nemeth E, Boudjema K, Turlin B, Troadec MB, Leroyer P, Ropert M, Jacquelinet S, Courselaud B, Ganz T, Brissot P, Loréal O. Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function. Blood. 2005;106:746-748.
Not in our library10.1182/blood-2004-12-4855
352.
Weizer-Stern O, Adamsky K, Amariglio N, Rachmilewitz E, Breda L, Rivella S, Rechavi G. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models. Amer J Hematol. 2006;81:479-483.
Not in our library10.1002/ajh.20549
353.
Weizer-Stern O, Adamsky K, Amariglio N, Levin C, Koren A, Breuer W, Rachmilewitz E, Breda L, Rivella S, Cabantchik ZI, Rechavi G. Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera. Br J Haematol. 2006;135:129-138.
Not in our library10.1111/j.1365-2141.2006.06258.x
354.
Weizer-Stern O, Adamsky K, Margalit O, Ashur-Fabian O, Givol D, Amariglio N, Rechavi G. Hepcidin, a key regulator of iron metabolism, is transcriptionally activated by p53. Br J Haematol. 2007;138:253-62.
Not in our library10.1111/j.1365-2141.2007.06638.x
355.
Sullivan JL. Macrophage iron, hepcidin, and atherosclerotic plaque stability. Exp Biol Med (Maywood). 2007;232:1014-20.
Not in our library10.3181/0703-mr-54
356.
Adamsky K, Weizer O, Amariglio N, Breda L, Harmelin A, Rivella S, Rachmilewitz E, Rechavi G. Decreased hepcidin mRNA expression in thalassemic mice. Br J Haematol. 2004;124:123-124.
Not in our library10.1046/j.1365-2141.2003.04734.x
357.
Flower DR, North AC, Sansom CE. The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta. 2000;1482:9-24.
Not in our library10.1016/s0167-4838(00)00148-5
358.
Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993;268:10425-32.
Not in our library
359.
Stoesz SP, Gould MN. Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. Oncogene. 1995;11:2233-41.
Not in our library
360.
Kjeldsen L, Cowland JB, Borregaard N. Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse. Biochim Biophys Acta. 2000;1482:272-83.
Not in our library10.1016/s0167-4838(00)00152-7
361.
Liu Q, Ryon J, Nilsen-Hamilton M. Uterocalin: a mouse acute phase protein expressed in the uterus around birth. Mol Reprod Dev. 1997;46:507-14.
Not in our library10.1002/(sici)1098-2795(199704)46:4<507::aid-mrd9>3.0.co;2-s
362.
Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10:1033-43.
Not in our library10.1016/s1097-2765(02)00708-6
363.
Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004;432:917-21.
Not in our library10.1038/nature03104
364.
Fluckinger M, Haas H, Merschak P, Glasgow BJ, Redl B. Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores. Antimicrob Agents Chemother. 2004;48:3367-72.
Not in our library10.1128/aac.48.9.3367-3372.2004
365.
Holmes MA, Paulsene W, Jide X, Ratledge C, Strong RK. Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. Structure. 2005;13:29-41.
Not in our library10.1016/j.str.2004.10.009
366.
Berger T, Togawa A, Duncan GS, Elia AJ, You-Ten A, Wakeham A, Fong HE, Cheung CC, Mak TW. Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proc Natl Acad Sci USA. 2006;103:1834-9.
Not in our library10.1073/pnas.0510847103
367.
Borregaard N, Cowland JB. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Biometals. 2006;19:211-215.
Not in our library10.1007/s10534-005-3251-7
368.
Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002;10:1045-56.
Not in our library10.1016/s1097-2765(02)00710-4
369.
Coles M, Diercks T, Muehlenweg B, Bartsch S, Zolzer V, Tschesche H, Kessler H. The solution structure and dynamics of human neutrophil gelatinase-associated lipocalin. J Mol Biol. 1999;289:139-57.
Not in our library10.1006/jmbi.1999.2755
370.
Tschesche H, Zolzer V, Triebel S, Bartsch S. The human neutrophil lipocalin supports the allosteric activation of matrix metalloproteinases. Eur J Biochem. 2001;268:1918-1928.
Not in our library10.1046/j.1432-1327.2001.02066.x
371.
Yan L, Borregaard N, Kjeldsen L, Moses MA. The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. J Biol Chem. 2001;276:37258-65.
Not in our library10.1074/jbc.m106089200
372.
Devarajan P, Mishra J, Supavekin S, Patterson LT, Steven Potter S. Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. Mol Genet Metab. 2003;80:365-76.
Not in our library10.1016/j.ymgme.2003.09.012
373.
Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534-43.
Not in our library10.1097/01.asn.0000088027.54400.c6
374.
Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365:1231-8.
Not in our library10.1016/s0140-6736(05)74811-x
375.
Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D'Agati V, Devarajan P, Barasch J. Endocytic delivery of lipoccalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. Journal of Clinical Investigation. 2005;115:610-621.
Not in our library10.1172/jci23056
376.
Herget-Rosenthal S. One step forward in the early detection of acute renal failure. Lancet. 2005;365:1205-1206.
Not in our library10.1016/s0140-6736(05)74787-5
377.
Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P. Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury. Pediatric Nephrology. 2006;21:989-994.
Not in our library10.1007/s00467-006-0146-y
378.
Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study · 2007
No notice
379.
Devarajan P. Update on mechanisms of ischemic acute kidney injury. Journal of the American Society of Nephrology. 2006;17:1503-1520.
Not in our library10.1681/asn.2006010017
380.
Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J. Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens. 2006;15:442-9.
Not in our library10.1097/01.mnh.0000232886.81142.58
381.
Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol. 2007;18:407-13.
Not in our library10.1681/asn.2006080882
382.
Mori K, Nakao K. Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. Kidney Int. 2007;71:967-70.
Not in our library10.1038/sj.ki.5002165
383.
Mitsnefes MM, Kathman TS, Mishra J, Kartal J, Khoury PR, Nickolas TL, Barasch J, Devarajan P. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol. 2007;22:101-8.
Not in our library10.1007/s00467-006-0244-x
384.
Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study · 2007
No notice
385.
Molitoris BA, Melnikov VY, Okusa MD, Himmelfarb J. Technology Insight: biomarker development in acute kidney injury–what can we anticipate? Nat Clin Pract Nephrol. 2008;4:154-65.
Not in our library10.1038/ncpneph0723
386.
Nickolas TL, O'Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med. 2008;148:810-9.
Not in our library10.7326/0003-4819-148-11-200806030-00003
387.
Malyszko J, Bachorzewska-Gajewska H, Sitniewska E, Malyszko JS, Poniatowski B, Dobrzycki S. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in non-diabetic patients with stage 2–4 chronic kidney disease. Ren Fail. 2008;30:625-8.
Not in our library10.1080/08860220802134607
388.
Devarajan P. NGAL in acute kidney injury: from serendipity to utility. Am J Kidney Dis. 2008;52:395-9.
Not in our library10.1053/j.ajkd.2008.07.008
389.
Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand J Clin Lab Invest Suppl. 2008;241:89-94.
Not in our library10.1080/00365510802150158
390.
Devireddy LR, Gazin C, Zhu X, Green MR. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell. 2005;123:1293-305.
Not in our library10.1016/j.cell.2005.10.027
391.
Richardson DR. 24p3 and its receptor: dawn of a new iron age? Cell. 2005;123:1175-7.
Not in our library10.1016/j.cell.2005.12.008
392.
Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett. 2005;579:773-7.
Not in our library10.1016/j.febslet.2004.12.031
393.
Roudkenar MH, Kuwahara Y, Baba T, Roushandeh AM, Ebishima S, Abe S, Ohkubo Y, Fukumoto M. Oxidative stress induced lipocalin 2 gene expression: Addressing its expression under the harmful conditions. Journal of Radiation Research. 2007;48:39-44.
Not in our library10.1269/jrr.06057
394.
Roudkenar MH, Halabian R, Ghasemipour Z, Roushandeh AM, Rouhbakhsh M, Nekogoftar M, Kuwahara Y, Fukumoto M, Shokrgozar MA. Neutrophil Gelatinase-associated Lipocalin acts as a protective factor against H2O2 toxicity. Arch Med Res. 2008;39:560-6.
Not in our library10.1016/j.arcmed.2008.05.003
395.
Gueler F, Gwinner W, Schwarz A, Haller H. Long-term effects of acute ischemia and reperfusion injury. Kidney International. 2004;66:523-527.
Not in our library10.1111/j.1523-1755.2004.761_11.x
396.
Sikorski EM, Hock T, Hill-Kapturczak N, Agarwal A. The story so far: molecular regulation of the heme oxygenase-1 gene in renal injury. Am J Physiol. 2004;286:F425-F441.
Not in our library10.1152/ajprenal.00297.2003
397.
Shah S. Role of iron in progressive renal disease. Am J Kidney Dis. 2001;37:S30-3.
Not in our library10.1053/ajkd.2001.20736
398.
Aigner F, Maier HT, Schwelberger HG, Wallnofer EA, Amberger A, Obrist P, Berger T, Mak TW, Maglione M, Margreiter R, Schneeberger S, Troppmair J. Lipocalin-2 regulates the inflammatory response during ischemia and reperfusion of the transplanted heart. Amer J Transplantation. 2007;7:779-788.
Not in our library10.1111/j.1600-6143.2006.01723.x
399.
Abergel RJ, Moore EG, Strong RK, Raymond KN. Microbial evasion of the immune system: structural modifications of enterobactin impair siderocalin recognition. J Am Chem Soc. 2006;128:10998-9.
Not in our library10.1021/ja062476+
400.
Fischbach MA, Lin H, Zhou L, Yu Y, Abergel RJ, Liu DR, Raymond KN, Wanner BL, Strong RK, Walsh CT, Aderem A, Smith KD. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc Natl Acad Sci USA. 2006;103:16502-7.
Not in our library10.1073/pnas.0604636103
401.
Abergel RJ, Clifton MC, Pizarro JC, Warner JA, Shuh DK, Strong RK, Raymond KN. The siderocalin/enterobactin interaction: a link between mammalian immunity and bacterial iron transport. J Am Chem Soc. 2008;130:11524-34.
Not in our library10.1021/ja803524w
402.
Cowland JB, Borregaard N. Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics. 1997;45:17-23.
Not in our library10.1006/geno.1997.4896
403.
Xu S, Venge P. Lipocalins as biochemical markers of disease. Biochim Biophys Acta. 2000;1482:298-307.
Not in our library10.1016/s0167-4838(00)00163-1
404.
Cowland JB, Sorensen OE, Sehested M, Borregaard N. Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1 beta, but not by TNF-alpha. J Immunol. 2003;171:6630-9.
Not in our library10.4049/jimmunol.171.12.6630
405.
Cowland JB, Muta T, Borregaard N. IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta. J Immunol. 2006;176:5559-66.
Not in our library10.4049/jimmunol.176.9.5559
406.
Elneihoum AM, Falke P, Axelsson L, Lundberg E, Lindgarde F, Ohlsson K. Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke. 1996;27:1734-8.
Not in our library10.1161/01.str.27.10.1734
407.
Elneihoum AM, Falke P, Hedblad B, Lindgarde F, Ohlsson K. Leukocyte activation in atherosclerosis: correlation with risk factors. Atherosclerosis. 1997;131:79-84.
Not in our library10.1016/s0021-9150(96)06077-7
408.
Falke P, Elneihoum AM, Ohlsson K. Leukocyte activation: relation to cardiovascular mortality after cerebrovascular ischemia. Cerebrovasc Dis. 2000;10:97-101.
Not in our library10.1159/000016037
409.
Hemdahl AL, Gabrielsen A, Zhu C, Eriksson P, Hedin U, Kastrup J, Thoren P, Hansson GK. Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arterioscler Thromb Vasc Biol. 2006;26:136-42.
Not in our library10.1161/01.atv.0000193567.88685.f4
410.
Stoesz SP, Friedl A, Haag JD, Lindstrom MJ, Clark GM, Gould MN. Heterogeneous expression of the lipocalin NGAL in primary breast cancers. Int J Cancer. 1998;79:565-72.
Not in our library10.1002/(sici)1097-0215(19981218)79:6<565::aid-ijc3>3.0.co;2-f
411.
Tong Z, Wu X, Ovcharenko D, Zhu J, Chen CS, Kehrer JP. Neutrophil gelatinase-associated lipocalin as a survival factor. Biochem J. 2005;391:441-8.
Not in our library10.1042/bj20051020
412.
Tong Z, Kunnumakkara AB, Wang H, Matsuo Y, Diagaradjane P, Harikumar KB, Ramachandran V, Sung B, Chakraborty A, Bresalier RS, Logsdon C, Aggarwal BB, Krishnan S, Guha S. Neutrophil gelatinase-associated lipocalin: a novel suppressor of invasion and angiogenesis in pancreatic cancer. Cancer Res. 2008;68:6100-8.
Not in our library10.1158/0008-5472.can-08-0540
413.
Weinberg ED. Iron out-of-balance: a risk factor for acute and chronic diseases. Hemoglobin. 2008;32:117-22.
Not in our library10.1080/03630260701680805
414.
CESDI. Confidential Enquiry into Stillbirths and Deaths in Infancy. 5th Annual Report. 1998.
Not in our library
415.
LaMarca BD, Gilbert J, Granger JP. Recent progress toward the understanding of the pathophysiology of hypertension during preeclampsia. Hypertension. 2008;51:982-8.
Not in our library10.1161/hypertensionaha.107.108837
416.
Redman CW, Sargent IL. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000;21:597-602.
Not in our library10.1053/plac.2000.0560
417.
DiFederico E, Genbacev O, Fisher SJ. Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. Am J Pathol. 1999;155:293-301.
Not in our library10.1016/s0002-9440(10)65123-1
418.
Leung DN, Smith SC, To KF, Sahota DS, Baker PN. Increased placental apoptosis in pregnancies complicated by preeclampsia. Am J Obstet Gynecol. 2001;184:1249-50.
Not in our library10.1067/mob.2001.112906
419.
Huppertz B, Kingdom JC. Apoptosis in the trophoblast–role of apoptosis in placental morphogenesis. J Soc Gynecol Investig. 2004;11:353-62.
Not in our library10.1016/j.jsgi.2004.06.002
420.
Harris LK, Keogh RJ, Wareing M, Baker PN, Cartwright JE, Aplin JD, Whitley GS. Invasive trophoblasts stimulate vascular smooth muscle cell apoptosis by a fas ligand-dependent mechanism. Am J Pathol. 2006;169:1863-74.
Not in our library10.2353/ajpath.2006.060265
421.
Heazell AE, Moll SJ, Jones CJ, Baker PN, Crocker IP. Formation of syncytial knots is increased by hyperoxia, hypoxia and reactive oxygen species. Placenta. 2007;28:S33-40.
Not in our library10.1016/j.placenta.2006.10.007
422.
Keogh RJ, Harris LK, Freeman A, Baker PN, Aplin JD, Whitley GS, Cartwright JE. Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death. Circ Res. 2007;100:834-41.
Not in our library10.1161/01.res.0000261352.81736.37
423.
Heazell AE, Lacey HA, Jones CJ, Huppertz B, Baker PN, Crocker IP. Effects of oxygen on cell turnover and expression of regulators of apoptosis in human placental trophoblast. Placenta. 2008;29:175-86.
Not in our library10.1016/j.placenta.2007.11.002
424.
Combs CA, Katz MA, Kitzmiller JL, Brescia RJ. Experimental preeclampsia produced by chronic constriction of the lower aorta: validation with longitudinal blood pressure measurements in conscious rhesus monkeys. Am J Obstet Gynecol. 1993;169:215-23.
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425.
Wisdom SJ, Wilson R, McKillop JH, Walker JJ. Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension. Am J Obs Gynecol. 1991;165:1701-1704.
Not in our library10.1016/0002-9378(91)90018-m
426.
Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest. 1996;97:540-50.
Not in our library10.1172/jci118447
427.
Benyo DF, Miles TM, Conrad KP. Hypoxia stimulates cytokine production by villous explants from the human placenta. J Clin Endocrinol Metab. 1997;82:1582-8.
Not in our library10.1210/jcem.82.5.3916
428.
Conrad KP, Benyo DF. Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol. 1997;37:240-9.
Not in our library10.1111/j.1600-0897.1997.tb00222.x
429.
Lefevre G, Berkane N, Uzan S, Etienne J. Preeclampsia and oxygen free radicals. Annales De Biologie Clinique. 1997;55:443-450.
Not in our library
430.
Conrad KP, Miles TM, Benyo DF. Circulating levels of immunoreactive cytokines in women with preeclampsia. Am J Reprod Immunol. 1998;40:102-11.
Not in our library10.1111/j.1600-0897.1998.tb00398.x
431.
Davidge ST. Oxidative stress and altered endothelial cell function in preeclampsia. Semin Reprod Endocrinol. 1998;16:65-73.
Not in our library10.1055/s-2007-1016254
432.
Mise H, Sagawa N, Matsumoto T, Yura S, Nanno H, Itoh H, Mori T, Masuzaki H, Hosoda K, Ogawa Y, Nakao K. Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia. J Clin Endocrinol Metab. 1998;83:3225-9.
Not in our library10.1210/jcem.83.9.5117
433.
Walker JJ. Antioxidants and inflammatory cell response in preeclampsia. Semin Reprod Endocrinol. 1998;16:47-55.
Not in our library10.1055/s-2007-1016252
434.
Walsh SW. Maternal-placental interactions of oxidative stress and antioxidants in preeclampsia. Seminars in Reproductive Endocrinology. 1998;16:93-104.
Not in our library10.1055/s-2007-1016256
435.
Caniggia I, Grisaru-Gravnosky S, Kuliszewsky M, Post M, Lye SJ. Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest. 1999;103:1641-50.
Not in our library10.1172/jci6380
436.
Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222:222-35.
Not in our library10.1177/153537029922200305
437.
Rinehart BK, Terrone DA, Lagoo-Deenadayalan S, Barber WH, Hale EA, Martin JN, Bennett WA. Expression of the placental cytokines tumor necrosis factor alpha, interleukin 1beta, and interleukin 10 is increased in preeclampsia. Am J Obstet Gynecol. 1999;181:915-20.
Not in our library10.1016/s0002-9378(99)70325-x
438.
Caniggia I, Mostachfi H, Winter J, Gassmann M, Lye SJ, Kuliszewski M, Post M. Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J Clin Invest. 2000;105:577-87.
Not in our library10.1172/jci8316
439.
Kharb S. Total free radical trapping antioxidant potential in pre-eclampsia. Int J Gynaecol Obstet. 2000;69:23-6.
Not in our library10.1016/s0020-7292(99)00198-8
440.
Tálosi G, Endreffy E, Túri S, Németh I. Molecular and genetic aspects of preeclampsia: State of the art. Mol Genet Metab. 2000;71:565-572.
Not in our library10.1006/mgme.2000.3099
441.
Walsh SW, Vaughan JE, Wang Y, Roberts LJ. Placental isoprostane is significantly increased in preeclampsia. FASEB J. 2000;14:1289-96.
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Stocker R, Keaney JF. New insights on oxidative stress in the artery wall. Journal of Thrombosis and Haemostasis. 2005;3:1825-1834.
Not in our library10.1111/j.1538-7836.2005.01370.x
771.
Stanley N, Stadler N, Woods AA, Bannon PG, Davies MJ. Concentrations of iron correlate with the extent of protein, but not lipid, oxidation in advanced human atherosclerotic lesions. Free Radical Biology and Medicine. 2006;40:1636-1643.
Not in our library10.1016/j.freeradbiomed.2005.12.031
772.
Watt F, Rajendran R, Ren MQ, Tan BKH, Halliwell B. A nuclear microscopy study of trace elements Ca, Fe, Zn and Cu in atherosclerosis. Nucl Instr Meth Phys Res B. 2006;249:646-652.
Not in our library
773.
Ferritina sérica e coronariopatia obstrutiva: correlação angiográfica Serum ferritin and obstructive coronary artery disease: angiographic correlation · 2007
Not checked
774.
Rajendran R, Ren M, Ning P, Tan Kwong Huat B, Halliwell B, Watt F. Promotion of atherogenesis by copper or iron–which is more likely? Biochem Biophys Res Commun. 2007;353:6-10.
Not in our library10.1016/j.bbrc.2006.11.038
775.
Kazi TG, Afridi HI, Kazi N, Jamali MK, Arain MB, Sarfraz RA, Jalbani N, Ansari R, Shah AQ, Memon AU, Khandhro GA. Distribution of zinc, copper and iron in biological samples of Pakistani myocardial infarction (1st, 2nd and 3rd heart attack) patients and controls. Clin Chim Acta. 2008;389:114-9.
Not in our library10.1016/j.cca.2007.12.004
776.
Sullivan JL. Iron in arterial plaque: A modifiable risk factor for atherosclerosis. Biochim Biophys Acta. 2008.
Not in our library10.1016/j.bbagen.2008.06.005
777.
Yuan XM, Li W. Iron involvement in multiple signaling pathways of atherosclerosis: a revisited hypothesis. Curr Med Chem. 2008;15:2157-72.
Not in our library10.2174/092986708785747634
778.
Matthews AJ, Vercellotti GM, Menchaca HJ, Bloch PH, Michalek VN, Marker PH, Murar J, Buchwald H. Iron and atherosclerosis: inhibition by the iron chelator deferiprone (L1). J Surg Res. 1997;73:35-40.
Not in our library10.1006/jsre.1997.5180
779.
Ponraj D, Makjanic J, Thong PSP, Tan BKH, Watt F. The onset of atherosclerotic lesion formation in hypercholesterolemic rabbits is delayed by iron depletion. FEBS Lett. 1999;459:218-222.
Not in our library10.1016/s0014-5793(99)01199-0
780.
Lee TS, Shiao MS, Pan CC, Chau LY. Iron-deficient diet reduces atherosclerotic lesions in ApoE-deficient mice. Circulation. 1999;99:1222-1229.
Not in our library10.1161/01.cir.99.9.1222
781.
Ren MQ, Rajendran R, Pan N, Tan BKH, Ong WY, Watt F, Halliwell B. The iron chelator desferrioxamine inhibits atherosclerotic lesion development and decreases lesion iron concentrations in the cholesterol-fed rabbit. Free Radical Biology and Medicine. 2005;38:1206-1211.
Not in our library10.1016/j.freeradbiomed.2005.01.008
782.
Ferrara DE, Taylor WR. Iron chelation and vascular function: in search of the mechanisms. Arterioscler Thromb Vasc Biol. 2005;25:2235-7.
Not in our library10.1161/01.atv.0000189303.45609.1f
783.
Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation. 1997;96:3300-7.
Not in our library10.1161/01.cir.96.10.3300
784.
de Valk B, Marx JJM. Iron, atherosclerosis, and ischemic heart disease. Arch Internal Med. 1999;159:1542-1548.
Not in our library10.1001/archinte.159.14.1542
785.
Zacharski LR, Chow B, Lavori PW, Howes PS, Bell MR, DiTommaso MA, Carnegie NM, Bech F, Amidi M, Muluk S. The Iron (Fe) and Atherosclerosis Study (FeAST): A pilot study of reduction of body iron stores in atherosclerotic peripheral vascular disease. American Heart Journal. 2000;139:337-345.
Not in our library10.1067/mhj.2000.102909
786.
Day SM, Duquaine D, Mundada LV, Menon RG, Khan BV, Rajagopalan S, Fay WP. Chronic iron administration increases vascular oxidative stress and accelerates arterial thrombosis. Circulation. 2003;107:2601-2606.
Not in our library10.1161/01.cir.0000066910.02844.d0
787.
Ren MQ, Watt F, Huat BTK, Halliwell B. Trace elemental distributions in induced atherosclerotic lesions using nuclear microscopy. Nuclear Instr Meth Phys Res B. 2003;210:336-342.
Not in our library
788.
Minqin R, Watt F, Huat BTK, Halliwell B. Correlation of iron and zinc levels with lesion depth in newly formed atherosclerotic lesions. Free Radical Biology and Medicine. 2003;34:746-752.
Not in our library10.1016/s0891-5849(02)01427-2
789.
You SA, Archacki SR, Angheloiu G, Moravec CS, Rao S, Kinter M, Topol EJ, Wang Q. Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis. Physiol Genomics. 2003;13:25-30.
Not in our library10.1152/physiolgenomics.00124.2002
790.
Zacharski LR, Gerhard GS. Atherosclerosis: a manifestation of chronic iron toxicity? Vascular Medicine. 2003;8:153-155.
Not in our library10.1191/1358863x03vm492ed
791.
Kallianpur AR. Iron and oxidative injury – A commentary on "Fatty acid-mediated iron translocation: A synergistic mechanism of oxidative injury" by D. Yao et al. Free Radical Biology and Medicine. 2005;39:1305-1309.
Not in our library10.1016/j.freeradbiomed.2005.07.014
792.
You SA, Wang Q. Ferritin in atherosclerosis. Clin Chim Acta. 2005;357:1-16.
Not in our library10.1016/j.cccn.2005.02.001
793.
Lapenna D, Pierdomenico SD, Ciofani G, Ucchino S, Neri M, Giamberardino MA, Cuccurullo F. Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. Free Rad Biol Med. 2007;42:492-498.
Not in our library10.1016/j.freeradbiomed.2006.11.014
794.
Marx JJ, Kartikasari AE, Georgiou NA. Can iron chelators influence the progression of atherosclerosis? Hemoglobin. 2008;32:123-34.
Not in our library10.1080/03630260701726871
795.
Paulsson J, Dadfar E, Held C, Jacobson SH, Lundahl J. Activation of peripheral and in vivo transmigrated neutrophils in patients with stable coronary artery disease. Atherosclerosis. 2007;192:328-34.
Not in our library10.1016/j.atherosclerosis.2006.08.003
796.
Rooyakkers TM, Stroes ES, Kooistra MP, van Faassen EE, Hider RC, Rabelink TJ, Marx JJ. Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo. Eur J Clin Invest. 2002;32:9-16.
Not in our library10.1046/j.1365-2362.2002.0320s1009.x
797.
Duffy SJ, Biegelsen ES, Holbrook M, Russell JD, Gokce N, Keaney JF, Vita JA. Iron chelation improves endothelial function in patients with coronary artery disease. Circulation. 2001;103:2799-804.
Not in our library10.1161/01.cir.103.23.2799
798.
Ishizaka N, Saito K, Mori I, Matsuzaki G, Ohno M, Nagai R. Iron chelation suppresses ferritin upregulation and attenuates vascular dysfunction in the aorta of angiotensin II-infused rats. Arterioscler Thromb Vasc Biol. 2005;25:2282-8.
Not in our library10.1161/01.atv.0000181763.57495.2b
799.
Saito K, Ishizaka N, Aizawa T, Sata M, Iso-o N, Noiri E, Mori I, Ohno M, Nagai R. Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-beta1 in the heart. Am J Physiol Heart Circ Physiol. 2005;288:H1836-43.
Not in our library10.1152/ajpheart.00679.2004
800.
Thomas SR, Schulz E, Keaney JF. Hydrogen peroxide restrains endothelium-derived nitric oxide bioactivity – Role for iron-dependent oxidative stress. Free Radical Biology and Medicine. 2006;41:681-688.
Not in our library10.1016/j.freeradbiomed.2006.05.012
801.
Zacharski LR, Chow BK, Howes PS, Shamayeva G, Baron JA, Dalman RL, Malenka DJ, Ozaki CK, Lavori PW. Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease – A randomized controlled trial. JAMA. 2007;297:603-610.
Not in our library10.1001/jama.297.6.603
802.
Shiesh SC, Chen CY, Lin XZ, Liu ZA, Tsao HC. Melatonin prevents pigment gallstone formation induced by bile duct ligation in guinea pigs. Hepatology. 2000;32:455-60.
Not in our library10.1053/jhep.2000.16332
803.
Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, Tan DX, Reiter RJ. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Dig Dis Sci. 2008;53:2592-603.
Not in our library10.1007/s10620-007-0195-5
804.
Robinson JG. Models for describing relations among the various statin drugs, low-density lipoprotein cholesterol lowering, pleiotropic effects, and cardiovascular risk. Am J Cardiol. 2008;101:1009-15.
Not in our library10.1016/j.amjcard.2007.11.060
805.
Prentice RL, Langer RD, Stefanick ML, Howard BV, Pettinger M, Anderson GL, Barad D, Curb JD, Kotchen J, Kuller L, Limacher M, Wactawski-Wende J. Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease. Am J Epidemiol. 2006;163:589-99.
Not in our library10.1093/aje/kwj079
806.
Couzin J. Cholesterol veers off script. Science. 2008;322:220-3.
Not in our library10.1126/science.322.5899.220
807.
Peterson RT. Chemical biology and the limits of reductionism. Nat Chem Biol. 2008;4:635-8.
Not in our library10.1038/nchembio1108-635
808.
Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001;7:687-92.
Not in our library10.1038/89058
809.
Arkin MR, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004;3:301-17.
Not in our library10.1038/nrd1343
810.
Bellosta S, Ferri N, Arnaboldi L, Bernini F, Paoletti R, Corsini A. Pleiotropic effects of statins in atherosclerosis and diabetes. Diabetes Care. 2000;23:B72-U5.
Not in our library
811.
Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000;6:1399-402.
Not in our library10.1038/82219
812.
Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;286:64-70.
Not in our library10.1001/jama.286.1.64
813.
LaRosa JC. Pleiotropic effects of statins and their clinical significance. American Journal of Cardiology. 2001;88:291.
Not in our library10.1016/s0002-9149(01)01643-5
814.
Takemoto M, Node K, Nakagami H, Liao YL, Grimm M, Takemoto Y, Kitakaze M, Liao JK. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. Journal of Clinical Investigation. 2001;108:1429-1437.
Not in our library10.1172/jci13350
815.
Liao JK. Beyond lipid lowering: the role of statins in vascular protection. Int J Cardiol. 2002;86:5-18.
Not in our library10.1016/s0167-5273(02)00195-x
816.
McFarlane SI, Muniyappa R, Francisco R, Sowers JR. Clinical review 145 – Pleiotropic effects of statins: Lipid reduction and beyond. J Clin Endocrinol Metab. 2002;87:1451-1458.
Not in our library10.1210/jcem.87.4.8412
817.
Undas A, Brozek J, Musial J. Anti-inflammatory and antithrombotic effects of statins in the management of coronary artery disease. Clin Lab. 2002;48:287-96.
Not in our library
818.
Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond lipid lowering–are they clinically relevant? Eur Heart J. 2003;24:225-48.
Not in our library10.1016/s0195-668x(02)00419-0
819.
Dichtl W, Dulak J, Frick M, Alber HF, Schwarzacher SP, Ares MPS, Nilsson J, Pachinger O, Weidinger F. HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells. Arteriosclerosis Thrombosis and Vascular Biology. 2003;23:58-63.
Not in our library10.1161/01.atv.0000043456.48735.20
820.
Mulhaupt F, Matter CM, Kwak BR, Pelli G, Veillard NR, Burger F, Graber P, Luscher TF, Mach F. Statins (HMG-CoA reductase inhibitors) reduce CD40 expression in human vascular cells. Cardiovasc Res. 2003;59:755-66.
Not in our library10.1016/s0008-6363(03)00515-7
821.
Wierzbicki AS, Poston R, Ferro A. The lipid and non-lipid effects of statins. Pharmacol Ther. 2003;99:95-112.
Not in our library10.1016/s0163-7258(03)00055-x
822.
Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004;109:39-43.
Not in our library10.1161/01.cir.0000131517.20177.5a
823.
Halcox JP, Deanfield JE. Beyond the laboratory: clinical implications for statin pleiotropy. Circulation. 2004;109:II42-8.
Not in our library10.1161/01.cir.0000129500.29229.92
824.
Liao JK. Statins: potent vascular anti-inflammatory agents. Int J Clin Pract Suppl. 2004;41-8.
Not in our library10.1111/j.1368-504x.2004.00375.x
825.
Schönbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors – Statins as antiinflammatory agents? Circulation. 2004;109:18-26.
Not in our library10.1161/01.cir.0000129505.34151.23
826.
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118.
Not in our library10.1146/annurev.pharmtox.45.120403.095748
827.
Elrod JW, Lefer DJ. The effects of statins on endothelium, inflammation and cardioprotection. Drug News Perspect. 2005;18:229-36.
Not in our library10.1358/dnp.2005.18.4.908656
828.
Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: Benefit beyond cholesterol reduction? A meta-regression analysis. J Amer Coll Cardiol. 2005;46:1855-1862.
Not in our library10.1016/j.jacc.2005.05.085
829.
Tsubouchi H, Inoguchi T, Sonta T, Sato N, Sekiguchi N, Kobayashi K, Sumimoto H, Utsumi H, Nawata H. Statin attenuates high glucose-induced and diabetes-induced oxidative stress in vitro and in vivo evaluated by electron spin resonance measurement. Free Radical Biology and Medicine. 2005;39:444-452.
Not in our library10.1016/j.freeradbiomed.2005.03.031
830.
Beckman JA, Creager MA. The nonlipid effects of statins on endothelial function. Trends Cardiovasc Med. 2006;16:156-62.
Not in our library10.1016/j.tcm.2006.03.003
831.
Carloni S, Mazzoni E, Cimino M, De Simoni MG, Perego C, Scopa C, Balduini W. Simvastatin reduces caspase-3 activation and inflammatory markers induced by hypoxia-ischemia in the newborn rat. Neurobiol Dis. 2006;21:119-26.
Not in our library10.1016/j.nbd.2005.06.014
832.
Grimes DS. Are statins analogues of vitamin D? Lancet. 2006;368:83-6.
Not in our library10.1016/s0140-6736(06)68971-x
833.
Paumelle R, Blanquart C, Briand O, Barbier O, Duhem C, Woerly G, Percevault F, Fruchart JC, Dombrowicz D, Glineur C, Staels B. Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway. Circ Res. 2006;98:361-9.
Not in our library10.1161/01.res.0000202706.70992.95
834.
Alegret M, Silvestre JS. Pleiotropic effects of statins and related pharmacological experimental approaches. Timely Top Med Cardiovasc Dis. 2007;11:E10.
Not in our library
835.
Farooqui AA, Ong WY, Horrocks LA, Chen P, Farooqui T. Comparison of biochemical effects of statins and fish oil in brain: the battle of the titans. Brain Res Rev. 2007;56:443-71.
Not in our library10.1016/j.brainresrev.2007.09.004
836.
Kuipers HF, Elsen PJ van den. Immunomodulation by statins: inhibition of cholesterol vs. isoprenoid biosynthesis. Biomed Pharmacother. 2007;61:400-7.
Not in our library10.1016/j.biopha.2007.06.005
837.
Lahera V, Goicoechea M, de Vinuesa SG, Miana M, de las Heras N, Cachofeiro V, Luno J. Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins. Curr Med Chem. 2007;14:243-8.
Not in our library10.2174/092986707779313381
838.
Paraskevas KI, Tzovaras AA, Briana DD, Mikhailidis DP. Emerging indications for statins: a pluripotent family of agents with several potential applications. Curr Pharm Des. 2007;13:3622-36.
Not in our library10.2174/138161207782794194
839.
Terblanche M, Almog Y, Rosenson R, Smith TS, Hackam DG. Statins and sepsis: multiple modifications at multiple levels. Lancet Infectious Diseases. 2007;7:358-368.
Not in our library10.1016/s1473-3099(07)70111-1
840.
Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008;14:37-44.
Not in our library10.1016/j.molmed.2007.11.004
841.
Wagner BK, Kitami T, Gilbert TJ, Peck D, Ramanathan A, Schreiber SL, Golub TR, Mootha VK. Large-scale chemical dissection of mitochondrial function. Nat Biotechnol. 2008;26:343-351.
Not in our library10.1038/nbt1387
842.
Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med. 2002;8:1257-62.
Not in our library10.1038/nm1102-1257
843.
Blake GJ, Ridker PM. Are statins anti-inflammatory? Curr Control Trials Cardiovasc Med. 2000;1:161-165.
Not in our library10.1186/cvm-1-3-161
844.
Diomede L, Albani D, Sottocorno M, Donati MB, Bianchi M, Fruscella P, Salmona M. In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. Arterioscler Thromb Vasc Biol. 2001;21:1327-32.
Not in our library10.1161/hq0801.094222
845.
Laufs U, Gertz K, Dirnagl U, Bohm M, Nickenig G, Endres M. Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice. Brain Res. 2002;942:23-30.
Not in our library10.1016/s0006-8993(02)02649-5
846.
Neuhaus O, Strasser-Fuchs S, Fazekas F, Kieseier BC, Niederwieser G, Hartung HP, Archelos JJ. Statins as immunomodulators: comparison with interferon-beta 1b in MS. Neurology. 2002;59:990-7.
Not in our library10.1212/wnl.59.7.990
847.
Rasmussen LM, Hansen PR, Nabipour MT, Olesen P, Kristiansen MT, Ledet T. Diverse effects of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase on the expression of VCAM-1 and E-selectin in endothelial cells. Biochem J. 2001;360:363-70.
Not in our library10.1042/0264-6021:3600363
848.
Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001;21:1712-9.
Not in our library10.1161/hq1101.098486
849.
Sukhova GK, Williams JK, Libby P. Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol. Arterioscler Thromb Vasc Biol. 2002;22:1452-8.
Not in our library10.1161/01.atv.0000030360.72503.56
850.
Scalia R, Stalker TJ. Microcirculation as a target for the anti-inflammatory properties of statins. Microcirculation. 2002;9:431-42.
Not in our library10.1038/sj.mn.7800168
851.
Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci. 2002;23:482-6.
Not in our library10.1016/s0165-6147(02)02077-1
852.
Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, 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.
Not in our library10.1038/nature01158
853.
Balk EM, Lau J, Goudas LC, Jordan HS, Kupelnick B, Kim LU, Karas RH. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med. 2003;139:670-82.
Not in our library10.7326/0003-4819-139-8-200310210-00011
854.
Blanco-Colio LM, Tuñon J, Martin-Ventura JL, Egido J. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int. 2003;63:12-23.
Not in our library10.1046/j.1523-1755.2003.00744.x
855.
Kwak BR, Mulhaupt F, Mach F. Atherosclerosis: anti-inflammatory and immunomodulatory activities of statins. Autoimmun Rev. 2003;2:332-8.
Not in our library10.1016/s1568-9972(03)00049-1
856.
Mason JC. Statins and their role in vascular protection. Clin Sci (Lond). 2003;105:251-66.
Not in our library10.1042/cs20030148
857.
Naidu BV, Woolley SM, Farivar AS, Thomas R, Fraga C, Mulligan MS. Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion. J Thorac Cardiovasc Surg. 2003;126:482-9.
Not in our library10.1016/s0022-5223(03)00699-8
858.
Pate GE, Tahir MN, Murphy RT, Foley JB. Anti-inflammatory effects of statins in patients with aortic stenosis. J Cardiovasc Pharmacol Ther. 2003;8:201-6.
Not in our library10.1177/107424840300800305
859.
Shishehbor MH, Aviles RJ, Brennan ML, Fu XM, Goormastic M, Pearce GL, Gokce N, Keaney JF, Penn MS, Sprecher DL, Vita JA, Hazen SL. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. JAMA. 2003;289:1675-1680.
Not in our library10.1001/jama.289.13.1675
860.
Stüve O, Youssef S, Dunn S, Slavin AJ, Steinman L, Zamvil SS. The potential therapeutic role of statins in central nervous system autoimmune disorders. Cell Mol Life Sci. 2003;60:2483-91.
Not in our library10.1007/s00018-003-3146-0
861.
Stüve O, Prod'homme T, Slavin A, Youssef S, Dunn S, Steinman L, Zamvil SS. Statins and their potential targets in multiple sclerosis therapy. Expert Opin Ther Targets. 2003;7:613-22.
Not in our library10.1517/14728222.7.5.613
862.
Stüve O, Youssef S, Steinman L, Zamvil SS. Statins as potential therapeutic agents in neuroinflammatory disorders. Curr Opin Neurol. 2003;16:393-401.
Not in our library10.1097/01.wco.0000073942.19076.d1
863.
Durant R, Klouche K, Delbosc S, Morena M, Amigues L, Beraud JJ, Canaud B, Cristol JP. Superoxide anion overproduction in sepsis: effects of vitamin e and simvastatin. Shock. 2004;22:34-9.
Not in our library10.1097/01.shk.0000129197.46212.7e
864.
Endres M, Laufs U. Effects of statins on endothelium and signaling mechanisms. Stroke. 2004;35:2708-11.
Not in our library10.1161/01.str.0000143319.73503.38
865.
Kunkel EJ, Dea M, Ebens A, Hytopoulos E, Melrose J, Nguyen D, Ota KS, Plavec I, Wang Y, Watson SR, Butcher EC, Berg EL. An integrative biology approach for analysis of drug action in models of human vascular inflammation. FASEB J. 2004;18:1279-81.
Not in our library10.1096/fj.04-1538fje
866.
McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, Capell HA, Sattar N. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004;363:2015-21.
Not in our library10.1016/s0140-6736(04)16449-0
867.
Rosenson RS. Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis. 2004;173:1-12.
Not in our library10.1016/s0021-9150(03)00239-9
868.
McInnes IB, McCarey DW, Sattar N. Do statins offer therapeutic potential in inflammatory arthritis? Ann Rheum Dis. 2004;63:1535-7.
Not in our library10.1136/ard.2004.022061
869.
Steffens S, Mach F. Anti-inflammatory properties of statins. Semin Vasc Med. 2004;4:417-22.
Not in our library10.1055/s-2004-869599
870.
Stoll LL, McCormick ML, Denning GM, Weintraub NL. Antioxidant effects of statins. Drugs Today (Barc). 2004;40:975-90.
Not in our library10.1358/dot.2004.40.12.872573
871.
Arnaud C, Braunersreuther V, Mach F. Toward immunomodulatory and anti-inflammatory properties of statins. Trends Cardiovasc Med. 2005;15:202-6.
Not in our library10.1016/j.tcm.2005.07.002
872.
Endres M. Statins and stroke. J Cereb Blood Flow Metab. 2005;25:1093-110.
Not in our library10.1038/sj.jcbfm.9600116
873.
Gaugler MH, Vereycken-Holler V, Squiban C, Vandamme M, Vozenin-Brotons MC, Benderitter M. Pravastatin limits endothelial activation after irradiation and decreases the resulting inflammatory and thrombotic responses. Radiat Res. 2005;163:479-87.
Not in our library10.1667/rr3302
874.
Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005;4:977-87.
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875.
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Perry G, Sayre LM, Atwood CS, Castellani RJ, Cash AD, Rottkamp CA, Smith MA. The role of iron and copper in the aetiology of neurodegenerative disorders – Therapeutic implications. CNS Drugs. 2002;16:339-352.
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Bush AI. The metallobiology of Alzheimer's disease. Trends Neurosci. 2003;26:207-214.
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Finefrock AE, Bush AI, Doraiswamy PM. Current status of metals as therapeutic targets in Alzheimer's disease. J Am Geriatr Soc. 2003;51:1143-8.
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Kalivendi SV, Cunningham S, Kotamraju S, Joseph J, Hillard CJ, Kalyanaraman B. alpha-synuclein up-regulation and aggregation during MPP+-induced apoptosis in neuroblastoma cells – Intermediacy of transferrin receptor iron and hydrogen peroxide. Journal of Biological Chemistry. 2004;279:15240-15247.
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1047.
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1049.
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Halliwell B. Oxidative stress and neurodegeneration: where are we now? Journal of Neurochemistry. 2006;97:1634-1658.
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Quintana C, Bellefqih S, Laval JY, Guerquin-Kern JL, Wu TD, Avila J, Ferrer I, Arranz R, Patino C. Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level. J Struct Biol. 2006;153:42-54.
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Whitnall M, Richardson DR. Iron: a new target for pharmacological intervention in neurodegenerative diseases. Semin Pediatr Neurol. 2006;13:186-97.
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Bartzokis G, Tishler TA, Lu PH, Villablanca P, Altshuler LL, Carter M, Huang D, Edwards N, Mintz J. Brain ferritin iron may influence age- and gender-related risks of neurodegeneration. Neurobiol Aging. 2007;28:414-23.
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1067.
Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X. Iron: the Redox-active center of oxidative stress in Alzheimer disease. Neurochem Res. 2007;32:1640-5.
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Gaasch JA, Lockman PR, Geldenhuys WJ, Allen DD, Schyf CJ Van der. Brain iron toxicity: differential responses of astrocytes, neurons, and endothelial cells. Neurochem Res. 2007;32:1196-208.
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Mandel S, Amit T, Bar-Am O, Youdim MB. Iron dysregulation in Alzheimer's disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents. Prog Neurobiol. 2007;82:348-60.
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1074.
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Petersen RB, Nunomura A, Lee HG, Casadesus G, Perry G, Smith MA, Zhu X. Signal transduction cascades associated with oxidative stress in Alzheimer's disease. J Alzheimers Dis. 2007;11:143-52.
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Reynolds A, Laurie C, Mosley RL, Gendelman HE. Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol. 2007;82:297-325.
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Singh C, Ahmad I, Kumar A. Pesticides and metals induced Parkinson's disease: involvement of free radicals and oxidative stress. Cell Mol Biol (Noisy-le-grand). 2007;53:19-28.
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Stankiewicz J, Panter SS, Neema M, Arora A, Batt CE, Bakshi R. Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics. 2007;4:371-86.
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Bush AI, Curtain CC. Twenty years of metallo-neurobiology: where to now? Eur Biophys J. 2008;37:241-5.
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Drechsel DA, Patel M. Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease. Free Radic Biol Med. 2008;44:1873-86.
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Rogers JT, Bush AI, Cho HH, Smith DH, Thomson AM, Friedlich AL, Lahiri DK, Leedman PJ, Huang X, Cahill CM. Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer's disease. Biochem Soc Trans. 2008;36:1282-7.
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Sayre LM, Perry G, Harris PLR, Liu YH, Schubert KA, Smith MA. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: A central role for bound transition metals. Journal of Neurochemistry. 2000;74:270-279.
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1500.
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1503.
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1508.
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1511.
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1512.
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1513.
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1514.
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1515.
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1516.
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1517.
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1518.
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1519.
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1521.
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1723.
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Youdim MBH, Fridkin M, Zheng HL. Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. Mech Ageing Dev. 2005;126:317-326.
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Bandyopadhyay S, Huang X, Cho H, Greig NH, Youdim MB, Rogers JT. Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5 ' untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine clioquinol, VK-28, and a piperazine chelator. Journal of Neural Transmission-Supplement. 2006;237-247.
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Limson J, Nyokong T, Daya S. The interaction of melatonin and its precursors with aluminium cadmium, copper iron, lead, and zinc: an adsorptive voltammetric study. J Pineal Res. 1998;24:15-21.
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1890.
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Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191-6.
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Kundu JK, Surh YJ. Molecular basis of chemoprevention by resveratrol: NF-kappaB and AP-1 as potential targets. Mutat Res. 2004;555:65-80.
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1897.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337-42.
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Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493-506.
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1899.
Kotha A, Sekharam M, Cilenti L, Siddiquee K, Khaled A, Zervos AS, Carter B, Turkson J, Jove R. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein. Mol Cancer Ther. 2006;5:621-9.
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Russo GL. Ins and outs of dietary phytochemicals in cancer chemoprevention. Biochem Pharmacol. 2007;74:533-44.
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Tsai SK, Hung LM, Fu YT, Cheng H, Nien MW, Liu HY, Zhang FB, Huang SS. Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats. J Vasc Surg. 2007;46:346-53.
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Chu YF, Sun J, Wu X, Liu RH. Antioxidant and antiproliferative activities of common vegetables. J Agric Food Chem. 2002;50:6910-6.
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Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H. Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. Int J Cancer. 2005;113:423-33.
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Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci USA. 2005;102:14813-8.
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Butelli E, Titta L, Giorgio M, Mock HP, Matros A, Peterek S, Schijlen EG, Hall RD, Bovy AG, Luo J, Martin C. Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors. Nat Biotechnol. 2008;26:1301-1308.
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Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC. Reversals of age-related declines in neuronal signal transduction cognitive, and motor behavioral deficits with blueberry spinach, or strawberry dietary supplementation. Journal of Neuroscience. 1999;19:8114-8121.
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Sweeney MI, Kalt W, MacKinnon SL, Ashby J, Gottschall-Pass KT. Feeding rats diets enriched in lowbush blueberries for six weeks decreases ischemia-induced brain damage. Nutritional Neuroscience. 2002;5:427-431.
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Joseph JA, Fisher DR, Bielinski D. Blueberry extract alters oxidative stress-mediated signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes. J Alzheimers Dis. 2006;9:35-42.
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Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: A review of their intracellular targets. Eur J Pharmacol. 2006;545:51-64.
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Kalt W, Joseph JA, Shukitt-Hale B. Blueberries and human health: a review of current reseach. J Amer Pomol Soc. 2007;61:151-160.
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Lau FC, Bielinski DF, Joseph JA. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J Neurosci Res. 2007;85:1010-7.
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Neto CC. Cranberry and blueberry: evidence for protective effects against cancer and vascular diseases. Mol Nutr Food Res. 2007;51:652-64.
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McAnulty SR, McAnulty LS, Nieman DC, Dumke CL, Morrow JD, Utter AC, Henson DA, Proulx WR, George GL. Consumption of blueberry polyphenols reduces exercise-induced oxidative stress compared to vitamin C. Nutrition Research. 2004;24:209-221.
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Longpré F, Garneau P, Christen Y, Ramassamy C. Protection by EGb 761 against beta-amyloid-induced neurotoxicity: Involvement of NF-kappa B, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation. Free Rad Biol Med. 2006;41:1781-1794.
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Ramassamy C, Longpré F, Christen Y. Ginkgo biloba extract (EGb 761) in Alzheimer's disease: Is there any evidence? Current Alzheimer Research. 2007;4:253-262.
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Wang Q, Simonyi A, Li WL, Sisk BA, Miller RL, MacDonald RS, Lubahn DE, Sun GY, Sun AY. Dietary grape supplement ameliorates cerebral ischemia-induced neuronal death in gerbils. Molecular Nutrition & Food Research. 2005;49:443-451.
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Curin Y, Andriantsitohaina R. Polyphenols as potential therapeutical agents against cardiovascular diseases. Pharmacological Reports. 2005;57:97-107.
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Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, Tsubono Y, Tsuji I. Green tea consumption and mortality due to cardiovascular disease cancer, and all causes in Japan – The Ohsaki Study. Jama-Journal of the American Medical Association. 2006;296:1255-1265.
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Fraser ML, Mok GS, Lee AH. Green tea and stroke prevention: emerging evidence. Complement Ther Med. 2007;15:46-53.
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Ikeda M, Suzuki C, Umegaki K, Saito K, Tabuchi M, Tomita T. Preventive effects of green tea catechins on spontaneous stroke in rats. Medical Science Monitor. 2007;13:BR40-BR45.
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Nelson SK, Bose SK, Grunwald GK, Myhill P, McCord JM. The induction of human superoxide dismutase and catalase in vivo: A fundamentally new approach to antioxidant therapy. Free Radical Biology and Medicine. 2006;40:341-347.
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Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413-20.
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Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22:11-23.
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Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005;81:230S-242S.
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Williamson G, Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr. 2005;81:243S-255S.
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Rechner AR, Kuhnle G, Bremner P, Hubbard GP, Moore KP, Rice-Evans CA. The metabolic fate of dietary polyphenols in humans. Free Radic Biol Med. 2002;33:220-35.
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Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002;22:19-34.
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Scalbert A, Morand C, Manach C, Remesy C. Absorption and metabolism of polyphenols in the gut and impact on health. Biomedicine & Pharmacotherapy. 2002;56:276-282.
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Passamonti S, Vrhovsek U, Vanzo A, Mattivi F. Fast access of some grape pigments to the brain. J Agric Food Chem. 2005;53:7029-34.
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Serra H, Mendes T, Bronze MR, Simplicio AL. Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones. Bioorg Med Chem. 2008;16:4009-18.
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