Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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The Effects of Oxidative Stress Induced by Aluminum on Cellular Macromolecules in the Hippocampus and Cerebral Cortex of Rats

알루미늄을 투여한 흰쥐의 해마와 대뇌피질에서 Reactive Oxygen Species 생성으로 인한 생체거대분자의 산화적 손상

  • 문철진 (의료법인 녹십자의료재단) ;
  • 고현철 (한양대학교 의과대학 약리학교실) ;
  • 신인철 (한양대학교 의과대학 약리학교실) ;
  • 이은희 (의료법인 녹십자의료재단) ;
  • 문해란 (의료법인 녹십자의료재단)
  • Published : 2004.09.01
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Abstract

This work aimed to study the effectiveness of cellular oxidative parameter (malondial-dehyde, protein carbonyl, and 8-hydroxy-2'deoxyguanosine). The experimental groups were aluminum treated rats and control rats. Aluminum treatd rats were given intraperitoneally aluminum nitrate nonahydrate ($Al^{3+}$, 0.2 mmol/kg) daily for 30 days except Sunday. Control rats were injected 1 ml of saline. After the dose, rats were decapitated and hippocampus and cerebral cortex were removed. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation), protein carbonyl (index of protein oxidation), 8-hydroxy-2'-deoxy-guanosine (8-OHdG, index of DNA oxidation), reduced glutathione (GSH) levels as well as glutathione reductase (GR) and catalase. AI concentrations in the tissues were also measured. All results were corrected by tissue protein levels. The results were as followed; 1. The concentrations of AI in the cortex and hippocampus were significantly higher in the AI-treated rats than in the control rats. 2. Antioxidative enzyme's activity, catalase and GR, were significantly higher in the AI-treated rats than the control rats. GSH levels were also higher in the AI-treated rats. 3. MDA, protein carbonyl, and 8-OHdG concentration of AI-treated rats were significantly higher than those of control rats. 4. The concentrations of antioxidants, and oxidative stress parameter were correlated with the concentrations of AI in hippocampus and cerebral cortex. Catalase and GR activity were also correlated with the concentration of AI. Based on these results, it can be suggested that intraperitoneally injected AI was accumulated in the brain and induced the increase of antioxidant levels and antioxidative enzyme activity. Also, the oxidative products of cellular macromolecules are significantly related to tissue AI concentration. Therefore MDA, protein carbonyl, and 8-OHdG are useful markers for oxidative stress on cellular macromolecules.

Keywords

References

  1. Alfrey, A.C., Legendre, G.R. and Kaehny, W.D. (1976): The dialysis encephalopathy syndrome. Possible aluminum intoxication. New Engl. J. Med., 294, 184-188
  2. Ames, B.N. (1989): Endogeneous oxidative DNA damage, aging, and cancer. Free Radical Res. Commun., 7, 121-128
  3. Chung, M.H., Kim, H.S., Ohtsuka, E., Kasai, H., Yamamoto, F. and Nishimura, S. (1991): An endonuclease activity in human polymorphonuclear neutrophils that removes 8hydroxyguanine residues from DNA. Biochem. Biophys. Res. Commun., 178, 1472-1478
  4. Connor, J.R. and Fine, R.E. (1986): The distribution of transferrin immunoreactivity in the rat central nervous system. Brain Res., 368, 319-328
  5. Deloncle, R. and Guillard, O. (1990): Mechanism of Alzheimer's disease: arguments for a neurotransmitter-aluminum complex implication. Neurochem. Res., 15, 1239-1245
  6. Deloncle, R., Huguet, F., Babin, P., Fernandez, B., Quellard, N. and Guillard, O. (1999): Chronic administration of aluminum L-glutamate in young mature rats: effects in iron levels and lipid peroxdiation in selected brain areas. Toxicology Letters, 10, 65-73
  7. EI-Maraghy, S.A., Gad, M.Z., Fahim, A.T. and Hamdy, M.A. (2001): Effect of cadmium and aluminum intake in the antioxidant status and lipid peroxidation in rat tissues. J. Biochem. Molecular Toxicology, 15, 207-214 https://doi.org/10.1002/jbt.18
  8. Flaten, T.P., Alfrey, A.C., Birchall, J.D., Savory, J. and Yokel, R.A. (1996): Status and future concerns of clinical and environmental aluminum toxicology. J. Toxicol. Environ. Health, 48, 527-541 https://doi.org/10.1080/009841096161050
  9. Fleming, J. and Joshi, J.G. (1997): Ferritin: isolation of aluminum- ferritin complex from brain. Proc. Natl. Acad. Sci.USA, 84, 7866-7870
  10. Floyd, R.A. (1990): Role of oxgen free radicals in carcinogenesis and brain ischemia. FASEB, 4, 2587-2597
  11. Floyd, R.A., Watson, J.J, Harris, J., West, M. and Wong, P.K. (1986): Formation of 8-hydroxy- deoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promotor, tetradeconylphorbolacetate. Biochem. Biophys. Res. Commun., 137, 841-846
  12. Fraga, C.G., Shigenaga, M.K., Park, J.W., Degan, P. and Ames, B.N. (1990): Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine. Proc. Natl. Acad. Sci. USA, 87, 4533-4537
  13. Fulton, B. and Jeffry, E.H. (1994): The temporal relationship between hepatic glutathione loss, heme oxygenase induction and cytochrome P-450 loss following intraperitoneal aluminum administraion to mice. Toxicol. App. Pharmacol., 127, 291-297
  14. Garruto, R.M. (1991): Pacific paradigms of environmentallyinduced neurological disorders: clinical, epidemiological, and molecular perspectives. Neurotoxicology, 12, 347-378
  15. Girotti, A.W. (1985): Mechanism of lipid peroxidation. J. Free Rad. BioI. Med., 1, 87-95 https://doi.org/10.1016/0748-5514(85)90011-X
  16. Golub, M.S., Han, B., Keen, C.L. and Gershwin, M.E. (1992): Effect of dietary aluminum excess and manganese deficiency on neurobehavioral endpoints in adult mice. Toxicol. App. Pharmacol., 112, 154-160
  17. Good, P.F., Olanow, C.W and Perl, D.P. (1992): Neuromelanin- containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. Brain Res., 593, 343-346
  18. Goyer, R.A., Klaassen, C.D. and Waalkes, M.P. (1995): Metal Toxicology. Academic Press, London, pp. 199-235
  19. Gupta, R.C. (1984): Nonrandom binding of the carcinogen Nhydroxy- 2-acetyl-aminofluorene to repetitive sequences of rat liver DNA in vivo. Proc. Natl. Acad. Sci. USA, 81, 6943-6947
  20. Gupta, A. and Shukla, G.S. (1995): Effect of chronic aluminum exposure in the levels of conjugated dienes and enzymatic antioxidants in hippocampus and whole brain of rats. Bull. Environ. Contam. Toxicol., 55, 716-722
  21. Halliwell, B. and Gutteridge J.M.C. (1998): Oxidative stress: adaptation, damage, repair, and death. Free Radicals in Biology and Medicine. Oxford university press, New York, pp. 246-350
  22. Janzen, E.G. (1980): A critical review of spin trapping in biological systems. In Free radicals in Biology, Academic press, New York, pp. 115-154
  23. Kappus, H. (1985): in OXidative stress. Academic press, New York, pp. 273-310
  24. Kamiya, H., Murata-Kamiya, N., Fujimuro, M. and Kido, K. (1995): Comparison of incorporation and extension of neucleotides in vitro opposite 8-hydroxyguanine (7,8-dihydro- 8-oxoguanine) in hot spots of the c-Ha-ras gene. Jpn. J. Cancer Res., 86, 270-276
  25. Keilin, D. (1966): In the history of cell respiration and cytochrome. Cambridge University Press, London, pp. 132
  26. Landsberg, J.P., Mc Donald, B. and Watt, F. (1992): Absence of aluminum in neuritic plaque cores in Alzheimer's disease. Nature, 360, 65-68 https://doi.org/10.1038/360065a0
  27. Levine, R.L., Garland, D., Oliver, C.N., Amici, A., Climent, J., Lenz, A.G., Ahn, B.W., Shaltiel, S. and Stadtman, E.R. (1990): Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol., 186, 464-478
  28. Lovell, M.A., Gabbita, S.P. and Markesbery, W.R. (1999): Increased DNA oxidation and decreased levels of repair products in Alzheimer's disease ventricular CSF. J. Neurochem., 72, 771-776 https://doi.org/10.1046/j.1471-4159.1999.0720771.x
  29. Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951): Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265-275
  30. Markesberry, W.R. (1997): Oxidative stress hypothesis in Alzheimer's disease. Free Rad. Biol. Med., 23, 134-147
  31. McLachlan, D.R.C. (1995): Aluminum and the risk for Alzheimer's disease. Environmetrics, 6, 233-275 https://doi.org/10.1002/env.3170060303
  32. Oliver, C.N., Stark-Reed, P., Stadtman, E.R., Liu, G.L., Carney, J.M. and Floyd, R.A. (1990): Ischemia/reperfusion induced oxidative damage to proteins in gerbil brain. Proc. Natl. Acad. Sci. USA, 87, 5144-5147
  33. Renard, J.L., Felton, D. and Bequet, D. (1994): Post-otoneurosurgery aluminum encephalophathy. Lancet, 344, 63-64
  34. Rosen, D.R., Siddique, T., FigJewiez, D.A. and Sapp, P. (1993): Mutation in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 362, 59-62 https://doi.org/10.1038/362059a0
  35. Sian J., Dexter, D.T., Lees, A.J., Daniel, S., Agid, Y., JavoyAgid, F., Jenner, P. and Marsden, C.D. (1994): Alteration in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol., 36, 348-355
  36. Sies, H. (1986): Oxidative stress: introductory remarks. In Oxidative stress, Academic. Orlando, Florida. pp. 1-8
  37. Steinbrecher, U.P., Lougheed, M., Kwan, W.-C. and Dirks, M. (1989): Recognition of oxidized low density lipoprotein by the scavenger receptor of macrophages results from derivatization of apolipoprotiens B by products of fatty acid peroxidation. J. Biol. Chem., 264, 15216-15223
  38. Thomas, J.P., Maiorino, M., Ursini, F. and Girotti, A.W. (1990): Protective action of phospholipid hydroxide glutathione peroxidase against membrane-damaging lipid peroxidation. J. Biol. Chem., 265, 454-461
  39. Uchida, K. and Stadtmand, E.R. (1992): Modification of histidine residues in proteins by reaction with 4-hydroxynonenal. Proc. Natl. Acad. Sci. USA, 89, 4544-4548
  40. Verstraeten, S.V., Nogueira, L.V., Schreier, S. and Oteiza, P.I. (1995): ${Sc}^{3+},{Ga}^{3+},{In}^{3+},Y^{3+},and {Be}^{3+}$ promote changes in membrane physical properties and facilitate ${Fe}^{2+}$-initiated lipid peroxidation. Arch. Biochem. Biophys., 322, 284-290
  41. Verstraeten, S.V., Keen, C.L., Golub, M.S. and Oteiza, P.I. (1998): Membrane composition can -influence the rate of ${Al}^{3+}$-mediated lipid oxidation: effect of galactolipids. Biochem. J., 333, 833-838
  42. Weinstock, M. (1995): The pharmacotheraphy of Alzheimer's disease based on the cholinergic hypothesis: an uptake. Neurodegeneration, 4, 349-356 https://doi.org/10.1006/neur.1995.0042
  43. Yokel, R.A, Ackrill, P. and Burgess, E. (1996): Prevention and treatment of aluminum toxicity including chelation therapy: status and research needs. J. Toxicol. Environ. Health, 48, 667-683 https://doi.org/10.1080/009841096161131