Neurochemical Roles of Copper as Antioxidant or Prooxidant

  • Joseph R. Prohaska


The biological reactivity of copper is the basis for both its essentiality and toxicity. Prior to the advent of modern medicine, drug design, and therapeutics, there is a long historical documentation of the use of copper salts in ointments for over 2000 years. The biological activity of copper was unknown at the time but was used for a wide variety of maladies including diseases of the skin, various infections, and recoveries from neurological disorders (Deuschle and Weser, 1985). Toxic properties of copper were also recognized as copper sulfate was used as a murder weapon and a suicidal agent.


Copper Deficiency Copper Toxicity Copper Status Menkes Disease Extracellular Superoxide Dismutase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allain, P., and Krari, N., 1991, Diethyldithiocarbamate, copper and neurological disorders, Life Sci. 48:291–299.PubMedCrossRefGoogle Scholar
  2. Allen, K. G. D., Arthur, J. R., Morrice, P. C., Nicol, F., and Mills, C. F., 1988, Copper deficiency and tissue glutathione concentration in the rat, Proc. Soc. Exp. Biol. Med. 187:38–43.PubMedGoogle Scholar
  3. Alt, E. R., Sternlieb, I., and Goldfischer, S., 1990, The cytopathology of metal overload, Int. Rev. Exp. Pathol. 31:165–188.PubMedGoogle Scholar
  4. Anzil, A. P., Herrlinger, H., Blinzinger, K., and Heldrich, A., 1974, Ultrastructure of brain and nerve biopsy tissue in Wilson disease, Arch. Neurol. 31:94–100.PubMedCrossRefGoogle Scholar
  5. Aust, S. D., Morehouse, L. A., and Thomas, C. E., 1985, Role of metals in oxygen radical reactions, J. Free Radicals Biol. Med. 1:3–25.CrossRefGoogle Scholar
  6. Barnea, A., Hartter, D. E., and Cho, G., 1989, High-affinity uptake of 67Cu into a veratridine-releasable pool in brain tissue, Am. J. Physiol. 257:C315-C322.Google Scholar
  7. Bradbury, A. F., and Smyth, D. G., 1991, Peptide amidation, Trends Biochem. Sci. 16:112–115.PubMedCrossRefGoogle Scholar
  8. Bremner, I., and Beattie, J. H., 1990, Metallothionein and the trace minerals, Ann. Rev. Nutr. 10:63–83.CrossRefGoogle Scholar
  9. Chan, P. H., Chu, L., Chen, S. F., Carlson, E. J., and Epstein, C. J., 1990, Reduced neurotoxicity in transgenic mice overexpressing human copper-zinc-superoxide dismutase, Stroke 2:111–80–111–82.Google Scholar
  10. Ceballos-Picot, I., Nicole, A., Clément, M., Bourre, J.-M., and Sinet, P.-M., 1992, Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase, Mut. Res. 275:281–293.CrossRefGoogle Scholar
  11. Connor, J. R., Tucker, P., Johnson, M., and Snyder, B., 1993, Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer’s disease, Neurosci. Lett. 159(1–2):88–90.PubMedCrossRefGoogle Scholar
  12. Danks, D. M., Campbell, P. E., Stevens, B. J., Mayne, V., and Cartwright, E., 1972, Menkes’ kinky hair syndrome, Pediatrics 50:188–201.PubMedGoogle Scholar
  13. Davis, G. K., and Mertz, W., 1987, Copper, in: Trace Elements in Human and Animal Nutrition, Volume 1 (W. Mertz, ed.), Academic Press, New York, pp. 301–364.Google Scholar
  14. Delmaestro, E., and Trombetta, L. D., 1995, The effects of disulfiram on the hippocampus and cerebellum of the rat brain: A study on oxidative stress, Toxicol. Lett. 75:235–243.PubMedCrossRefGoogle Scholar
  15. Deuschle, U., and Weser, U., 1985, Copper and inflammation, in: Progress in Clinical Biochemistry and Medicine, Volume 2 (E. Baulieu, D. T. Forman, L. Jaenicke, J. A. Kellen, Y. Nagai, G. F. Springer, L. Träger, L. Will-Shahab, and J. L. Wittliff, eds.), Springer-Verlag, New York, pp. 97–130.Google Scholar
  16. Dexter, D. T, Carayon, A., Javoy-Agid, F., Agid, Y, Wells, F R., Daniel, S. E., Lees, A. J., Jenner, P., and Marsden, C. D., 1991, Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia, Brain 114:1953–1975.PubMedCrossRefGoogle Scholar
  17. Donaldson, J., St-Pierre, T., Minnich, J., and Barbeau, A., 1971, Seizures in rats associated with divalent cation inhibition of Na+-K+-ATP’ase, Can. J. Biochem. 49:1217–1224.PubMedCrossRefGoogle Scholar
  18. Dougherty, J. J., and Hoekstra, W. G., 1982, Effects of vitamin E and selenium on copper-induced lipid peroxidation in vivo and on acute copper toxicity, Proc. Soc. Exp. Biol. Med. 169:201–208.PubMedGoogle Scholar
  19. Eipper, B. A., and Mains, R. E., 1988, Peptide α-amidation, Ann. Rev. Physiol. 50:333–344.CrossRefGoogle Scholar
  20. Feller, D. J., and O’Dell, B. L., 1980, Dopamine and norepinephrine in discrete areas of the copper-deficient rat brain, J. Neurochem. 34:1259–1263.PubMedCrossRefGoogle Scholar
  21. French, J. H., Sherard, E. S., Lubell, H., Brotz, M., and Moore, C. L., 1972, Trichopoliodystrophy. Report of a case and biochemical studies, Arch. Neurol. 26:229–244.PubMedCrossRefGoogle Scholar
  22. Furuta, A., Price, D. L., Pardo, C. A., Troncoso, J. C., Xu, Z. S., Taniguchi, N., and Martin, L. J., 1995, Localization of superoxide dismutases in Alzheimer’s disease and Down’s syndrome neocortex and hippocampus, Am. J. Pathol. 2:357–367.Google Scholar
  23. Gasull, T., Giralt, M., Hernandez, J., Martinez, P., Bremner, I., and Hidalgo, J., 1994, Regulation of metallothionein concentrations in rat brain: Effect of glucocorticoids, zinc, copper, and endotoxin, Am. J. Physiol. 266:E760-E767.Google Scholar
  24. Gutteridge, J. M. C., 1984, Copper-phenanthroline-induced site-specific oxygen-radical damage to DNA, Biochem. J. 218:983–985.PubMedGoogle Scholar
  25. Halliwell, B., 1992, Reactive oxygen species and the central nervous system, J. Neurochem. 59:1609–1623.PubMedCrossRefGoogle Scholar
  26. Hesse, L., Beher, D., Masters, C. L., and Multhaup, G., 1994, The ßA4 amyloid precursor protein binding to copper, FEBS Lett. 349:109–116.PubMedCrossRefGoogle Scholar
  27. Hidalgo, J., Garcia, A., Oliva, A. M., Giralt, M., Gasull, T, Gonzalez, B., Milnerowicz, H., Wood, A., and Bremner, I., 1994, Effect of zinc, copper and glucocorticoids on metallothionein levels of cultured neurons and astrocytes from rat brain, Chem. Biol. Interact. 93:197–219.PubMedCrossRefGoogle Scholar
  28. Howell, J. McC, and Mercer, J. F. B., 1994, The pathology and trace element status of the toxic milk mutant mouse, J. Comp. Pathol. 110:37–47.PubMedCrossRefGoogle Scholar
  29. Howell, J. McC, Blakemore, W. F, Gopinath, C., Hall, G. A., and Parker, J. H., 1974, Chronic copper poisoning and changes in the central nervous system of sheep, Acta Neuropath. 29:9–24.PubMedCrossRefGoogle Scholar
  30. Ishino, H., Mii, T, Hayashi, Y., Saito, A., and Otsuki, S., 1972, A case of Wilson’s disease with enormous cavity formation of cerebral white matter, Neurology 22:905–909.PubMedCrossRefGoogle Scholar
  31. Janes, S. M., Mu, D., Wemmer, D., Smith, A. J., Kaur, S., Maltby, D., Burlingame, A. L., and Klinman, J. P., 1990, A new redox cofactor in eukaryotic enzymes: 6-hydroxydopa at the active site of bovine serum amine oxidase, Science 248:981–987.PubMedCrossRefGoogle Scholar
  32. Johnson, M. A., Fischer, J. G., and Kays, S. E., 1992, Is copper an antioxidant nutrient?, Crit. Rev. Food Sci. Nutr. 32:1–31.PubMedCrossRefGoogle Scholar
  33. Kaler, S. G., Goldstein, D. S., Holmes, C., Salerno, J. A., and Gahl, W A., 1993, Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease, Ann. Neurol. 33:171–175.PubMedCrossRefGoogle Scholar
  34. Kodama, H., Okabe, I., Yanagisawa, M., Nomiyama, H., Nomiyama, K., Nose, O., and Kamoshita, S., 1988, Does CSF copper level in Wilson disease reflect copper accumulation in the brain?, Pediatr. Neurol. 4:35–37.PubMedCrossRefGoogle Scholar
  35. Komoly, S., Hudson, L. D., Webster, H.DeF, and Bondy, C. A., 1992, Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination, Proc. Natl. Acad. Sci. USA 89:1894–1898.PubMedCrossRefGoogle Scholar
  36. Kubat, W. D., and Prohaska, J. R., 1996, Copper status and ascorbic acid concentrations in rats, Nutr. Res. 16:237–243.CrossRefGoogle Scholar
  37. Lawrence, R. A., and Jenkinson, S. G., 1987, Effects of copper deficiency on carbon tetrachloride-induced lipid peroxidation, J. Lab. Clin. Med. 109:134–140.PubMedGoogle Scholar
  38. Levenson, C. W., and Janghorbani, M., 1994, Long-term measurement of organ copper turnover in rats by continuous feeding of a stable isotope, Anal. Biochem. 221:243–249.PubMedCrossRefGoogle Scholar
  39. Lew, R. A., Clarke, I. J., and Smith, A. I., 1992, Distribution and characterization of peptidylglycine α-amidating monooxygenase activity in the ovine brain and hypothalamo-pituitary axis, Endocrinology 130:994–1000.PubMedCrossRefGoogle Scholar
  40. Liao, Z., Medeiros, D. M., McCune, S. A., and Prochaska, L. J., 1995, Cardiac levels of fibronectin, laminin, isomyosins, and cytochrome c oxidase on weanling rats are more vulnerable to copper deficiency than those of postweanling rats, J. Nutr. Biochem. 6:385–391.PubMedCrossRefGoogle Scholar
  41. Linder, M. C., 1991, Biochemistry of Copper, Plenum Press, New York.Google Scholar
  42. Under, M. C., and Moor, J. R., 1977, Plasma ceruloplasmin: Evidence for its presence in and uptake by heart and other organs of the rat, Biochim. Biophys. Acta 499:329–336.CrossRefGoogle Scholar
  43. Loeffler, D. A., DeMaggio, A. J., Juneau, P. L., Brickman, C. M., Mashour, G. A., Finkelman, J. H., Pomara, N., and LeWitt, P. A., 1994, Ceruloplasmin is increased in cerebrospinal fluid in Alzheimer’s disease but not Parkinson’s disease, Alzheimer Disease and Associated Disorders 8:190–197.PubMedCrossRefGoogle Scholar
  44. Mains, R. E., Myers, A. C., and Eipper, B. A., 1985, Hormonal, drug, and dietary factors affecting peptidyl glycine α-amidating monooxygenase activity in various tissues of the adult male rat, Endocrinology 116:2505–2515.PubMedCrossRefGoogle Scholar
  45. Marklund, S. L., 1990, Expression of extracellular superoxide dismutase by human cell lines, Biochem. J. 266:213–219.PubMedGoogle Scholar
  46. Miller, D. S., and O’Dell, B. L., 1987, Milk and casein-based diets for the study of brain catecholamines in copper-deficient rats, J. Nutr. 117:1890–1897.PubMedGoogle Scholar
  47. Montine, T. J., Farris, D. B., and Graham, D. G., 1995, Covalent crosslinking of neurofilament proteins by oxidized catechols as a potential mechanism of Lewy body formation, J. Neuropathol. Exp. Neurol. 54:311–319.PubMedCrossRefGoogle Scholar
  48. Morita, A., Kimura, M., and Itokawa, Y., 1994a, Changes with age in the mineral status in brain of female SAMPI and SAMR1, in: The SAM Model of Senescence (T. Takeda, ed.), Elsevier Science, New York, pp. 317–320.Google Scholar
  49. Morita, A., Kimura, M., and Itokawa, Y, 1994b, The effect of aging on the mineral status of female mice, Biol. Trace Elem. Res. 42:165–177.PubMedCrossRefGoogle Scholar
  50. Morita, H., Ikeda, S., Yamamoto, K., Morita, S., Yoshida, K., Nomoto, S., Kato, M., and Yanagisawa, N., 1995, Hereditary ceruloplasmin deficiency with hemosiderosis: A clinicopathological study of a Japanese family, Ann. Neurol. 37:646–656.PubMedCrossRefGoogle Scholar
  51. O’Dell, B. L., and Prohaska, J. R., 1983, Biochemical aspects of copper deficiency in the nervous system, in: Neurobiology of the Trace Elements, Volume 1 (I. E. Dreosti, and R. M. Smith, eds.), Humana Press, Clifton, New Jersey, pp. 41–81.Google Scholar
  52. Ohtsuki, T., Matsumoto, M., Suzuki, K., Taniguchi, N., and Kamada, T., 1993, Effect of transient forebrain ischemia on superoxide dismutases in gerbil hippocampus, Brain Res. 620:305–309.PubMedCrossRefGoogle Scholar
  53. Oury, T. D., Ho, Y.-S., Piantadosi, C. A., and Crapo, J. D., 1992, Extracellular superoxide dismutase, nitric oxide, and central nervous system O2 toxicity, Proc. Natl. Acad. Sci. USA 89:9715–9719.PubMedCrossRefGoogle Scholar
  54. Owen, Jr. C. A., 1981, Copper Deficiency and Toxicity, Noyes Publications, Park Ridge, New Jersey.Google Scholar
  55. Owen, Jr. C. A., Dickson, E. R., Goldstein, N. P., Baggenstoss, A. H., and McCall, J. T., 1977, Hepatic subcellular distribution of copper in primary biliary cirrhosis, Mayo Clin. Proc. 52:73–80.PubMedGoogle Scholar
  56. Pletcher, J. M., and Banting, L. F., 1983, Copper deficiency in piglets characterized by spongy myelopathy and degenerative lesions in the great blood vessels, J. South Afr. Vet. Assoc. 54:43–46.Google Scholar
  57. Powell, S. R., and Wapnir, R. A., 1994, Adventitious redox-active metals in Krebs-Henseleit buffer can contribute to Langendorff heart experimental results, J. Mol. Cell. Cardiol. 26:769–778.PubMedCrossRefGoogle Scholar
  58. Prohaska, J. R., 1987, Functions of trace elements in brain metabolism, Physiol. Rev. 67:858–901.PubMedGoogle Scholar
  59. Prohaska, J. R., 1988, Biochemical functions of copper in animals, in: Essential and Toxic Trace Elements in Human Health and Disease (A. S. Prasad, ed.), Alan R. Liss, New York, pp. 105–124.Google Scholar
  60. Prohaska, J. R., 1990, Biochemical changes in copper deficiency, J. Nutr. Biochem. 1:452–461.PubMedCrossRefGoogle Scholar
  61. Prohaska, J. R., and Bailey, W. R., 1993a, Copper deficiency during neonatal development alters mouse brain catecholamine levels, Nutr. Res. 13:331–338.CrossRefGoogle Scholar
  62. Prohaska, J. R., and Bailey, W. R., 1993b, Persistent regional changes in brain copper, cuproenzymes and catecholamines following perinatal copper deficiency in mice, J. Nutr. 123:1226–1234.PubMedGoogle Scholar
  63. Prohaska, J. R., and Bailey, W. R., 1994, Regional specificity in alterations of rat brain copper and catecholamines following perinatal copper deficiency, J. Neurochem. 63:1551–1557.PubMedCrossRefGoogle Scholar
  64. Prohaska, J. R., and Bailey, W. R., 1995a, Persistent neurochemical changes following perinatal copper deficiency in rats, J. Nutr. Biochem. 6:275–280.CrossRefGoogle Scholar
  65. Prohaska, J. R., and Bailey, W. R., 1995b, Alterations of rat brain peptidylglycine α-amidating mono-oxygenase and other cuproenzyme activities following perinatal copper deficiency, Proc. Soc. Exp. Biol. Med. 210:107–116.PubMedGoogle Scholar
  66. Prohaska, J. R., and Cox, D. A., 1983, Decreased brain ascorbate levels in copper-deficient mice and in brindled mice, J. Nutr. 113:2623–2629.PubMedGoogle Scholar
  67. Prohaska, J. R., and Smith, T. L., 1982, Effect of dietary or genetic copper deficiency on brain catecholamines, trace metals and enzymes in mice and rats, J. Nutr. 112:1706–1717.PubMedGoogle Scholar
  68. Prohaska, J. R., and Wells, W. W., 1974, Copper deficiency in the developing rat brain: A possible model for Menkes’ steely-hair disease, J. Neurochem. 23:91–98.PubMedCrossRefGoogle Scholar
  69. Prohaska, J. R., and Wells, W. W., 1975, Copper deficiency in the developing rat brain: Evidence for abnormal mitochondria, J. Neurochem. 25:221–228.PubMedCrossRefGoogle Scholar
  70. Prohaska, J. R., Bailey, W. R., and Lear, P. M., 1995, Copper deficiency alters rat peptidylglycine α-amidating monooxygenase activity, J. Nutr. 125:1447–1454.PubMedGoogle Scholar
  71. Przedborski, S., Jackson-Lewis, V., Kostic, V., Carlson, E., Epstein, C. J., and Cadet, J. L., 1992, Superoxide dismutase, catalase, and glutathione peroxidase activities in copper/zinc-superoxide dismutase transgenic mice, J. Neurochem. 58:1760–1767.PubMedCrossRefGoogle Scholar
  72. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O’Regan, J. P., Deng, H.-X., Rahmani, Z., Krizus, A., McKenna-Yasek, D., Cayabyab, A., Gaston, S. M., Berger, R., Tanzi, R. E., Halperin, J. J., Herzfeldt, B., Van den Bergh, R., Hung, W.-Y., Bird, T., Deng, G., Mulder, D. W, Smyth, C., Laing, N. G., Soriano, E., Pericak-Vance, M. A., Haines, J., Rouleau, G. A., Gusella, J. S., Horvitz, H. R., and Brown, Jr., R. H., 1993, Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature 362:59–62.PubMedCrossRefGoogle Scholar
  73. Rowley, D. A., and Halliwell, B., 1983, Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals in the presence of copper salts: A physiologically significant reaction? Arch. Biochem. Biophys. 225(1):279–284.PubMedCrossRefGoogle Scholar
  74. Saari, J. T., Dickerson, F. D., and Habib, M. P., 1990, Ethane production in copper-deficient rats, Proc. Soc. Exp. Biol. Med. 195:30–33.PubMedGoogle Scholar
  75. Sato, M., Sugiyama, T., Daimon, T., and Iijima, K., 1994, Histochemical evidence for abnormal copper distribution in the central nervous system of LEC mutant rat, Neurosci. Lett. 17:97–100.CrossRefGoogle Scholar
  76. Schafer, M. K.-H., Stoffers, D. A., Eipper, B. A., and Watson, S. J., 1992, Expression of peptidylglycine α-amidating monooxygenase (EC in the rat central nervous system, J. Neurosci. 12:222–234.PubMedGoogle Scholar
  77. Simpson, J. A., Cheeseman, K. H., Smith, S. E., and Dean, R. T., 1988, Free-radical generation by copper ions and hydrogen peroxide, Biochem. J. 254:519–523.PubMedGoogle Scholar
  78. Sokol, R. J., Devereaux, M., Mierau, G. W., Hambidge, K. M., and Shikes, R. H., 1990, Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload, Gastroenterology 99:1061–1071.PubMedGoogle Scholar
  79. Sokol, R. J., Twedt, D., McKim, Jr., J. M., Devereaux, M. W, Karrer, F. M., Kam, I., von Steigman, G., Narkewicz, M. R., Bacon, B. R., Britton, R. S., and Neuschwander-Tetri, B. A., 1994, Oxidant injury to hepatic mitochondria in patients with Wilson’s disease and Bedlington terriers with copper toxicosis, Gastroenterology 107:1788–1798.PubMedGoogle Scholar
  80. Sparaco, M., Hirano, A., Hirano, M., DiMauro, S., and Bonilla, E., 1993, Cytochrome c oxidase deficiency and neuronal involvement in Menkes’ kinky hair disease: Immunohistochemical study, Brain Pathol. 3:349–354.PubMedCrossRefGoogle Scholar
  81. Su, L.-C, Ravanshad, S., Owen, Jr., C. A., McCall, J. T., Zollman, P. E., and Hardy, R. M., 1982, A comparison of copper-loading disease in Bedlington terriers and Wilson’s disease in humans, Am. J. Physiol. 243:G226-G230.Google Scholar
  82. Sugawara, N., Ikeda, T., Sugawara, C., Kohgo, Y., Kato, J., and Takeichi, N., 1992, Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis, Brain Res. 588:287–290.PubMedCrossRefGoogle Scholar
  83. Sun, S. H.-H., and O’Dell, B. L., 1992a, Low copper status of rats affects polyunsaturated fatty acid composition of brain phospholipids, unrelated to neuropathology, J. Nutr. 122:65–73.PubMedGoogle Scholar
  84. Sun, S. H.-H., and O’Dell, B. L., 1992b, Elevated striatal levels of glial fibrillary acidic protein associated with neuropathology in copper-deficient rats, J. Nutr. Biochem. 3:503–509.CrossRefGoogle Scholar
  85. Tanaka, H., Kasama, T., Inomata, K., and Nasu, F, 1990, Abnormal movements in brindled mutant mouse heterozygotes: As related to the development of their offspring—biochemical and morphological studies, Brain Dev. 12:284–292.PubMedCrossRefGoogle Scholar
  86. Tanzi, R. E., Petrukhin, K., Chernov, L, Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., and Gilliam, T. C., 1993, The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene, Nature Genet. 5:344–350.PubMedCrossRefGoogle Scholar
  87. Traystman, R. J., Kirsch, J. R., and Koehler, R. C., 1991, Oxygen radical mechanisms of brain injury following ischemia and reperfusion, J. Appl. Physiol. 71:1185–1195.PubMedGoogle Scholar
  88. Uchida, Y., Takio, K., Titani, K., Ihara, Y., and Tomonaga, M., 1991, The growth inhibitory factor that is deficient in the Alzheimer’s disease brain is a 68 amino acid metallothionein-like protein, Neuron 7:331–341.CrossRefGoogle Scholar
  89. Walshe, J. M., and Gibbs, K. R., 1987, Brain copper in Wilson’s disease, Lancet (II): 1030.CrossRefGoogle Scholar
  90. Yamaguchi, Y, Heiny, M. E., Shimizu, N., Aoki, T., and Gitlin, J. D., 1994, Expression of the Wilson disease gene is deficient in the Long-Evans Cinnamon rat, Biochem. J. 301:1–4.PubMedGoogle Scholar
  91. Yamamoto, F., Kasai, H., Togashi, Y, Takeichi, N., Hori, T., and Nishimura, S., 1993, Elevated level of 8-hydroxydeoxyguanosine in DNA of liver, kidneys, and brain of Long-Evans Cinnamon rats, Jpn. J. Cancer Res. 84(5):508–511.PubMedCrossRefGoogle Scholar
  92. Yang, G., Chan, P. H., Chen, J., Carlson, E., Chen, S. F., Weinstein, P., Epstein, C. J., and Kamii, H., 1994, Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia, Stroke 25:165–170.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Joseph R. Prohaska
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, School of MedicineUniversity of Minnesota-DuluthDuluthUSA

Personalised recommendations