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Copper: toxicological relevance and mechanisms

Archives of Toxicology volume 88, pages 1929–1938 (2014)Cite this article

Abstract

Copper (Cu) is a vital mineral essential for many biological processes. The vast majority of all Cu in healthy humans is associated with enzyme prosthetic groups or bound to proteins. Cu homeostasis is tightly regulated through a complex system of Cu transporters and chaperone proteins. Excess or toxicity of Cu, which is associated with the pathogenesis of hepatic disorder, neurodegenerative changes and other disease conditions, can occur when Cu homeostasis is disrupted. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced cellular toxicity. Recently, altered cellular events, including lipid metabolism, gene expression, alpha-synuclein aggregation, activation of acidic sphingomyelinase and release of ceramide, and temporal and spatial distribution of Cu in hepatocytes, as well as Cu-protein interaction in the nerve system, have been suggested to play a role in Cu toxicity. However, whether these changes are independent of, or secondary to, an altered cellular redox state of Cu remain to be elucidated.

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References

  • Armstrong C, Leong W, Lees GJ (2001) Comparative effects of metal chelating agents on the neuronal cytotoxicity induced by copper (Cu2), iron (Fe3) and zinc in the hippocampus. Brain Res 892:51–62

    PubMed  Article  CAS  Google Scholar 

  • Barceloux DG (1999) Copper. J Toxicol Clin Toxicol 37:217–230

    PubMed  Article  CAS  Google Scholar 

  • Boal AK, Rosenzweig AC (2009). Structural biology of copper trafficking. Chem Rev 109:4760–4779

  • Bleackley MR, Macgillivray RT (2011) Transition metal homeostasis: from yeast to human disease. Biometals 24:785–809

    PubMed  Article  CAS  Google Scholar 

  • Braiterman LT, Murthy A, Jayakanthan S, Nyasae L, Tzeng E, Gromadzka G, Wolf TB, Lutsenko S, Hubbard AL (2014) Distinct phenotype of a Wilson disease mutation reveals a novel trafficking determinant in the copper transporter ATP7B. Proc Natl Acad Sci U S A 111:E1364–E1373

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Bremner I (1998) Manifestations of copper excess. Am J Clin Nutr 67:1069S–1073S

    PubMed  CAS  Google Scholar 

  • Brewer GJ (2007) A brand new mechanism for copper toxicity. J Hepatol 47:621–622

    PubMed  Article  CAS  Google Scholar 

  • Buettner G (1993) The packing order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol and ascorbate. Arch Biochem Biophys 300:535–543

    PubMed  Article  CAS  Google Scholar 

  • Burkhead JL, Gray LW, Lutsenko S (2011) Systems biology approach to Wilson’s disease. Biometals 24:455–466

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Burkitt MJ (2001) A critical overview of the chemistry of copper-dependent low density lipoprotein oxidation: roles of lipid hydroperoxides, alpha-tocopherol, thiols and ceruloplasmin. Arch Biochem Biophys 394:117–135

    PubMed  Article  CAS  Google Scholar 

  • Caliceti C, Nigro P, Rizzo P, Ferrari R (2014) ROS, Notch, and Wnt signaling pathways: crosstalk between three major regulators of cardiovascular biology. BioMed Res Int Article ID 318714, 8 pages, 10.1155/2014/318714

  • Chow CK (1979) Nutritional influence on cellular antioxidant defense systems. Am J Clin Nutr 32:1066–1081

    PubMed  CAS  Google Scholar 

  • Chow CK (1991) Vitamin E and oxidative stress. Free Radic Biol Med 11:215–232

    PubMed  Article  CAS  Google Scholar 

  • Chow CK, Chow-Johnson HS (2013) Antioxidant function and health implication of vitamin E. Open Nutr J. 6:1–6

    Article  Google Scholar 

  • D’Autréaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    PubMed  Article  Google Scholar 

  • de Romaña DL, Olivares M, Uauy R, Araya M (2011) Risks and benefits of copper in light of new insights of copper homeostasis. J Trace Elem Med Biol 25:3–13

    PubMed  Article  Google Scholar 

  • Divertie MB, Owen CA Jr, Barham SS, Ludwig J (1982) Accumulation of radionuclide-labeled platelets and fibrinogen in paraquat-damaged rat lungs. Am Rev Respir Dis 125:574–578

    PubMed  CAS  Google Scholar 

  • Evans PJ, Halliwell B (1994) Measurement of iron and copper in biological settings: bleomycin and Cu-phenanthroline assays. Methods Enzymol 233:82–92

    PubMed  Article  CAS  Google Scholar 

  • Fields M, Lewis CG, Bureau I (2001) Aspirin reduces blood cholesterol in copper-deficient rats: a potential antioxidant agent. Metabolism 50:558–561

    PubMed  Article  CAS  Google Scholar 

  • Food and Nutrition Board and Institute of Medicine (2006) Dietary Reference Intakes. In: Otten JJ, Hellwig JP, Meyers LD (eds) The essential guide to nutrient requirements, copper. National Academy Press, Washington, pp 304–311

    Google Scholar 

  • Fuentealba IC, Mullins JE, Aburto EM, Lau JC, Cherian GM (2000) Effect of age and sex on liver damage due to excess dietary copper in Fischer 344 rats. Clin Toxicol 38:709–717

    Article  CAS  Google Scholar 

  • Gaetke LM, Chow CK (2003) Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicol 189:147–163

    Article  CAS  Google Scholar 

  • Georgopoulos PG, Wang SW, Georgopoulos IG, Yonone-Lioy MJ, Lioy PJ (2006) Assessment of human exposure to copper: a case study using the NHEXAS database. J Expo Sci Environ Epidemiol 16:397–409

    PubMed  Article  CAS  Google Scholar 

  • Goodman VL, Brewer GJ, Merajver SD (2004) Copper deficiency as an anti-cancer strategy. Endocr Relat Cancer 11:255–263

    PubMed  Article  CAS  Google Scholar 

  • Gupta A, Lutsenko S (2009) Human copper transporters: mechanism, role in human diseases and therapeutic potential. Future Med Chem 1:1125–1142

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Haidari M, Javadi E, Kadkhodaee M, Sanati A (2001) Enhanced susceptibility to oxidation and diminished vitamin E content of LDL from patients with stable coronary artery disease. Clin Chem 47:1234–1240

    PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JM (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1–14

    PubMed  CAS  PubMed Central  Google Scholar 

  • Harris ED (1992) Copper as a cofactor and regulator of Cu, zinc superoxide dismutase. J Nutr 122:636S–640S

    Google Scholar 

  • Harris E (1993) The transport of copper. In: Prasad AS (ed) Essential and toxic trace elements in human health and disease: an update. Wiley-Liss, New York, pp 163–179

    Google Scholar 

  • Hasan NM, Lutsenko S (2012) Regulation of copper transporters in human cells. Curr Top Membr Transp 69:137–161

    Article  CAS  Google Scholar 

  • Hatori Y, Clasen S, Hasan NM, Barry AN, Lutsenko S (2012) Functional partnership of the copper export machinery and glutathione balance in human cells. J Biol Chem 287:26678–26687

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Hayashi M, Kuge T, Endoh D, Nakayama K, Arikawa J, Takazawa A, Okui T (2000) Hepatic copper accumulation induces DNA strand breaks in the liver cells of Long/Evans Cinnamon strain rats. Biochem Biophys Res Commun 276:174–178

    PubMed  Article  CAS  Google Scholar 

  • Huster D, Lutsenko S (2007) Wilson disease: not just a copper disorder. Analysis of a Wilson disease model demonstrates the link between copper and lipid metabolism. Mol BioSyst 3:816–824

    PubMed  Article  CAS  Google Scholar 

  • Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicol 283:65–87

    Article  CAS  Google Scholar 

  • Kadiiska MB, Hanna PM, Jordan SJ, Mason RP (1993) Electron spin resonance evidence for free radical generation in copper-treated vitamin E- and selenium-deficient rats: invivo spin-trapping investigation. Mol Pharmacol 44:222–227

    PubMed  CAS  Google Scholar 

  • Kawanishi S, Inoe S, Yamamoto K (1989) Hydroxyl radical and singlet oxygen production and DNA damage induced by carcinogenic metal compounds and hydrogen peroxide. Biol Trace Elem Res 21:367–372

    PubMed  Article  CAS  Google Scholar 

  • Kelner GS, Lee M, Clark ME, Maciejewski D, McGrath D, Rabizadeh S, Lyons T, Bredesen D, Jenner P, Maki RA (2000) The copper transport protein Atox1 promotes neuronal survival. J Biol Chem 275:580–584

    PubMed  Article  CAS  Google Scholar 

  • Kim H, Wu X, Lee J (2013) SLC31 (CTR) family of copper transporters in health and disease. Mol Asp Med 34:561–570

    Article  CAS  Google Scholar 

  • Lang F, Ullrich S, Gulbins E (2011) Ceramide formation as a target in beta-cell survival and function. Expert Opin Ther Targets 15:1061–1071

    PubMed  Article  CAS  Google Scholar 

  • Letelier ME, Faúndez M, Jara-Sandoval J, Molina-Berríos A, Cortés-Troncoso J, Aracena-Parks P, Marín-Catalán R (2009) Mechanisms underlying the inhibition of the cytochrome P450 system by copper ions. J Appl Toxicol 29:695–702

    PubMed  Article  CAS  Google Scholar 

  • Letelier ME, Sánchez-Jofré S, Peredo-Silva L, Cortés-Troncoso J, Aracena-Parks P (2010) Mechanisms underlying iron and copper ions toxicity in biological systems: pro-oxidant activity and protein-binding effects. Chem Biol Interact 188:220–227

    PubMed  Article  CAS  Google Scholar 

  • Levy MA, Tsai Y, Reaume A, Bray TM (2001) Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol 281:L172–L182

    PubMed  CAS  Google Scholar 

  • Liang Q, Dedon PC (2001) Cu(II)/H2O2-induced DNA damage is enhanced by packaging of DNA as a nucleosome. Chem Res Toxicol 14:416–422

    PubMed  Article  CAS  Google Scholar 

  • Linder MC, Hazegh-Azam M (1996) Copper biochemistry and molecular biology. Am J Clin Nutr 63:797S–811S

    PubMed  CAS  Google Scholar 

  • Linder MC, Wooten L, Cerveza P, Cotton S, Shulze R, Lomeli N (1998) Copper transport. Am J Clin Nutr 67:965S–971S

    PubMed  CAS  Google Scholar 

  • Lippard SJ (1999) Free copper ions in the cell? Science 284:748–749

    PubMed  Article  CAS  Google Scholar 

  • Long YC, Tan TMC, Inoue T, Tang BL (2014) The biochemistry and cell biology of aging: metabolic regulation through mitochondrial signaling. Am J Physiol Endocrinol Metab 306:E581–E591

    PubMed  Article  CAS  Google Scholar 

  • Lucas LC, Lemons JE (1992) Biodegradation of restorative metallic systems. Adv Dent Res 6:32–37

    PubMed  CAS  Google Scholar 

  • Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY (2007a) Function and regulation of human copper-transporting ATPases. Physiol Rev 87:1011–1046

    PubMed  Article  CAS  Google Scholar 

  • Lutsenko S, LeShane ES, Shinde U (2007b) Biochemical basis of regulation of human copper-transporting ATPases. Arch Biochem Biophys 463:134–148

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Lynch SM, Frei B, Morrow JD, Roberts LJ, Xu A, Jackson T, Reyna R, Klevay LM, Vita JA, Keaney JF Jr (1997) Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation. Arterioscler Thromb Vasc Biol 17:2975–2981

    PubMed  Article  CAS  Google Scholar 

  • Marí M, Colell A, Morales A, Pañeda C, Varela-Nieto I, García-Ruiz C, Fernández-Checa JC (2004) Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. J Clin Invest 113:895–904

    PubMed  Article  PubMed Central  Google Scholar 

  • Medici V, Trevisan CP, D’Incà R, Barollo M, Zancan L, Fagiuoli S, Martines D, Irato P, Sturniolo GC (2006) Diagnosis and management of Wilson’s disease: results of a single center experience. J Clin Gastroenterol 40:936–941

    PubMed  Article  Google Scholar 

  • Multhaup G (1997) Amyloid precursor protein, copper, and Alzheimer’s disease. Biomed Pharmacother 51:105–111

    PubMed  Article  CAS  Google Scholar 

  • Multhaup G, Masters CL, Beyreuther K (1998) Oxidative stress in Alzheimer’s disease. Alzheimer Rep 1:147–154

    Google Scholar 

  • Multhaup G, Hesse L, Borchardt T, Ruppert T, Cappai R, Masters CL, Beyreuther LK (1999) Autoxidation of amyloid precursor protein and formation of reactive oxygen species. Adv Exp Med Biol 36:365–387

    CAS  Google Scholar 

  • Myers BM, Prendergast FG, Holman R, Kuntz SM, Larusso NF (1993) Alterations in hepatocytes lysosomes in experimental hepatic copper overload in rats. Gastroenterology 105:1814–1823

    PubMed  CAS  Google Scholar 

  • Ohhira M, Ono M, Sekiya C (1995) Changes in free radical metabolizing enzymes and lipid peroxides in the liver of Long-Evans with cinnamon-like coat rats. J Gastroenterol 30:619–623

    PubMed  Article  CAS  Google Scholar 

  • Okereke T, Sternlieb I, Morell AG, Scheinberg IH (1972) Systemic absorption of intrauterine copper. Science 177:358–360

    PubMed  Article  CAS  Google Scholar 

  • Olivares M, Méndez MA, Astudillo PA, Pizarro F (2008) Present situation of biomarkers for copper status. Am J Clin Nutr 88:859S–862S

    PubMed  CAS  Google Scholar 

  • Ossola JO, Groppa MD, Tomaro ML (1997) Relationship between oxidative stress and heme oxygenase induction by copper sulfate. Arch Biochem Biophys 337:332–337

    PubMed  Article  CAS  Google Scholar 

  • Pandit A, Bhave S (1996) Present interpretation of the role of copper in Indian childhood cirrhosis. Am J Clin Nutr 63:830S–835S

    PubMed  CAS  Google Scholar 

  • Pankit AN, Bhave SA (2002) Copper metabolic defects and liver disease: environmental aspects. J Gastroenterol Hepatol 17:S403–S407

    PubMed  Article  Google Scholar 

  • Pohl HR, Roney N, Abadin HG (2011) Metal ions affecting the neurological system. Met Ions Life Sci 8:247–262

    PubMed  CAS  Google Scholar 

  • Polishchuk R, Lutsenko S (2013) Golgi in copper homeostasis: a view from the membrane trafficking field. Histochem Cell Biol 140:285–295

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Powell SR (2000) The antioxidant properties of zinc. J Nutr 130:1447S–1454S

    PubMed  CAS  Google Scholar 

  • Prohaska JR (2008) Role of copper transporters in copper homeostasis. Am J Clin Nutr 88:826S–829S

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ralle M, Huster D, Vogt S, Schirrmeister W, Burkhead JL, Capps TR, Gray L, Lai B, Maryon E, Lutsenko S (2010) Wilson disease at a single cell level: intracellular copper trafficking activates compartment-specific responses in hepatocytes. J Biol Chem 285:30875–30883

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Rana SV (2008) Metals and apoptosis: recent developments. J Trace Elem Med Biol 22:262–284

    PubMed  Article  CAS  Google Scholar 

  • Rivera-Mancía S, Pérez-Neri I, Ríos C, Tristán-López L, Rivera-Espinosa L, Montes S (2010) The transition metals copper and iron in neurodegenerative diseases. Chem Biol Interact 186:184–199

    PubMed  Article  Google Scholar 

  • Rodriguez-Granillo A, Crespo A, Estrin DA, Wittung-Stafshede P (2010) Copper-transfer mechanism from the human chaperone Atox1 to a metal-binding domain of Wilson disease protein. J Phys Chem B 114:3698–3706

    PubMed  Article  CAS  Google Scholar 

  • Rosenzweig AC (2001) Copper delivery by metallochaperone proteins. Acc Chem Res 34:119–128

    PubMed  Article  CAS  Google Scholar 

  • Rossi L, Arciello M, Capo C, Rotilio G (2006) Copper imbalance and oxidative stress in neurodegeneration. Ital J Biochem 55:212–221

    PubMed  CAS  Google Scholar 

  • Sansinanea AS, Cerone SI, Streitenberger SA, Garcia C, Auza N (1998) Oxidative effect of hepatic copper overload. Acta Physiol Pharmacol Ther Latinoam 48:25–31

    PubMed  CAS  Google Scholar 

  • Santos EM, Ball JS, Williams TD, Wu H, Ortega F, van Aerle R, Katsiadaki I, Falciani F, Viant MR, Chipman JK, Tyler CR (2010) Identifying health impacts of exposure to copper using transcriptomics and metabolomics in a fish model. Environ Sci Technol 44:820–826

    PubMed  Article  CAS  Google Scholar 

  • Sayre LM, Perry G, Harris PLR, Liu YH, Schubert KA, Smith MA (2000) In situ oxidative catalysis by neurofibrillary tangles and senile in Alzheimer’s disease: a central role for bound transition metals. J Neurochem 74:270–279

    PubMed  Article  CAS  Google Scholar 

  • Sokol RJ, Devereaux M, Mierau G, Hambidge KM, Shikes H (1990) Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Gastroenterology 90:1061–1071

    Google Scholar 

  • Song M, Zhou Z, Chen T, Zhang J, McClain CJ (2011) Copper deficiency exacerbates bile duct ligation-induced liver injury and fibrosis in rats. J Pharmacol Exp Ther 339:298–306

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Squitti R, Bressi F, Pasqualetti P, Bonomini C, Ghidoni R, Binetti G, Cassetta E, Moffa F, Ventriglia M, Vernieri F, Rossini PM (2009) Longitudinal prognostic value of serum “free” copper in patients with Alzheimer’s disease. Neurology 72:50–55

    PubMed  Article  CAS  Google Scholar 

  • Stern BR (2010) Essentiality and toxicity in copper health risk assessment: overview, update and regulatory considerations. J Toxicol Environ Health A 73:114–127

    PubMed  Article  CAS  Google Scholar 

  • Strausak D, Mercer JF, Dieter HH, Stremmel W, Multhaup G (2001) Copper in disorders with neurological symptoms: Alzheimer’s, Menkes and Wilson diseases. Brain Res Bull 55:175–185

    PubMed  Article  CAS  Google Scholar 

  • Su LC, Ravanshad S, Owen CA Jr, McCall JT, Zollman PE, Hardy RM (1982) A comparison of copper-loading disease in Bedlington terriers and Wilson’s disease in humans. Am J Physiol 243:G226–G230

    PubMed  CAS  Google Scholar 

  • Trumbo P, Yates AA, Schlicker S, Poos M (2001) Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc 101:294–301

    PubMed  Article  CAS  Google Scholar 

  • Turnlund JR (1999) Copper. In: Shils ME, Olson JA, Shike M, Ross AC (eds) Modern nutrition in health and disease. Lippincott Williams and Wilkins, Baltimore

    Google Scholar 

  • Turnlund J, Scott K, Peiffer G, Jang A, Keyes W, Keen C, Sakanashi T (1997) Copper status of young men consuming a low-copper diet. Am J Clin Nutr 65:72–78

    PubMed  CAS  Google Scholar 

  • Turnlund JR, Keyes WR, Peiffer GL, Scott KC (1998) Copper absorption, excretion, and retention by young men consuming low dietary copper determined by using the stable isotope 65Cu. Am J Clin Nutr 67:1219–1225

    PubMed  CAS  Google Scholar 

  • Uauy R, Olivares M, Gonzalez M (1998) Essentiality of copper in humans. Am J Clin Nutr 67:952S–959S

    PubMed  CAS  Google Scholar 

  • Uauy R, Maass A, Araya M (2008) Estimating risk from copper excess in human populations. Am J Clin Nutr 88:867S–871S

    PubMed  CAS  Google Scholar 

  • United States Environmental Protection Agency. 2013. Basic Information about Copper in Drinking Water. http://water.epa.gov/drink/contaminants/basicinformation/copper.cfm. Updated December 19, 2013

  • Vilaplana J, Romaguera C, Grimalt F, Cornellana F (1991) New trends in the use of metals in jewelry. Contact Dermatitis 25:145–148

    PubMed  Article  CAS  Google Scholar 

  • Wang X, Moualla D, Wright JA, Brown DR (2010) Copper binding regulates intracellular alpha-synuclein localisation, aggregation and toxicity. J Neurochem 113:704–714

    PubMed  Article  CAS  Google Scholar 

  • Wee NKY, Weinstein DC, Fraser ST, Assinder SJ (2013) The mammalian copper transporters CTR1 and CTR2 and their roles in development and disease. Int J Biochem Cell Biol 45:960–963

    PubMed  Article  CAS  Google Scholar 

  • White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, Masters CL, Bush AI, Cappai R (2001) Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer’s-type neurodegenerative pathways. J Neurochem 76:1509–1520

    PubMed  Article  CAS  Google Scholar 

  • Wijmenga C, Müller T, Murli IS, Brunt T, Feichtinger H, Schönitzer D, Houwen RH, Müller W, Sandkuijl LA, Pearson PL (1998) Endemic Tyrolean infantile cirrhosis is not an allelic variant of Wilson’s disease. Eur J Hum Genet 6:624–628

    PubMed  Article  CAS  Google Scholar 

  • Winge DR, Mehra RK (1990) Host defenses against copper toxicity. Int Rev Exp Pathol 31:47–83

    PubMed  Article  CAS  Google Scholar 

  • Wright LM, Huster D, Lutsenko S, Wrba F, Ferenci P, Fimmel CJ (2009) Hepatocyte GP73 expression in Wilson disease. J Hepatol 51:557–564

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  • Yang CA, Chen YH, Ke SC, Chen YR, Huang HB, Lin TH, Chen YC (2011) Correlation of copper interaction, copper-driven aggregation, and copper-driven H2O2 formation with Aβ40 conformation. Int J Alzheimers Dis. doi:10.4061/2011/607861

    Google Scholar 

  • Zatta P, Drago D, Zambenedetti P, Bolognin S, Nogara E, Peruffo A, Cozzi B (2008) Accumulation of copper and other metal ions, and metallothionein I/II expression in the bovine brain as a function of aging. J Chem Neuroanat 36:1–5

    PubMed  Article  CAS  Google Scholar 

  • Zhang SSZ, Noordin MM, Rahman SOA, Haron MJ (2000) Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats. Vet Hum Toxicol 42:261–264

    PubMed  CAS  Google Scholar 

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Affiliations

  1. Department of Dietetics and Human Nutrition, University of Kentucky, Lexington, KY, 40506, USA

    Lisa M. Gaetke & Ching K. Chow

  2. Department of Pediatrics, Loyola University Medical Center, North Riverside, IL, 60154, USA

    Hannah S. Chow-Johnson

  3. Graduate Center for Toxicology, University of Kentucky, Lexington, KY, 40506, USA

    Ching K. Chow

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  1. Lisa M. Gaetke
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  2. Hannah S. Chow-Johnson
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  3. Ching K. Chow
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Correspondence to Ching K. Chow.

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Gaetke, L.M., Chow-Johnson, H.S. & Chow, C.K. Copper: toxicological relevance and mechanisms. Arch Toxicol 88, 1929–1938 (2014). https://doi.org/10.1007/s00204-014-1355-y

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Keywords

  • Copper homeostasis
  • Copper exposure
  • Copper toxicity
  • Reactive oxygen species