Abstract
Aluminum is suspected to play a role in several neurological disorders. Reactive oxygen species (ROS) lead to oxidative stress, which is thought to be a possible mechanism for neurological damage. Interactions between aluminum and iron, a known promoter of prooxidant events, were studied in cerebral tissues using a fluorescent probe to measure rates of generation of ROS. Al2(SO4)3 alone failed to stimulate ROS production over a wide range of concentrations (50–1000 μM). The aluminum-deferrioxamine chelate in the absence of iron could also not potentiate ROS formation. However, Al2(SO4)3 potentiated FeSO4-induced ROS, with a maximal effect at 10 μM Fe and 500 μM Al. Kaolin, a hydrated aluminum silicate, did not potentiate iron-induced ROS formation. Ferritin had a minor stimulatory effect on ROS generation, but this was not potentiated by the concurrent presence of Al2(SO4)3. Transferrin had no effect on basal rates of ROS generation, but when Al2(SO4)3 was also present, ROS production was enhanced. It is concluded that:
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1.
There is a potentiation of iron-induced ROS by aluminum salts;
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2.
Free or complexed aluminum alone is not a key producer of ROS; and
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3.
High rates of ROS production are unlikely to be owing to the displacement by aluminum iron from its biologically sequestered locations.
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Abbreviations
- DCFH-DA:
-
2′, 7′-dichlorofluorescin diacetate
- DCFH:
-
2′, 7′-dichlorofluorescin
- DCF:
-
2′, 7′-dichlorofluorescein
- ROS:
-
reactive oxygen species
References
Aruoma O. I., Halliwell B., Laughton M. J., Quinlan G. J., and Gutteridge J. M. C. (1989) The mechanism of initiation of lipid peroxidation. Evidence against a requirement for an iron (II)-iron(III) conplex.Biochem. J. 258, 617–620.
Bass D. A., Parce J. W., Dechatelet L. R., Szeda P., and Seeds M. C. (1983) Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation.J. Immunol. 130, 1910–1917.
Bradford M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of dye-binding.Anal. Biochem. 72, 248–254.
Dean J. A. (1979)Lange's Handbook of Chemistry, 12th ed., New York, McGraw-Hill, p. 55.
Dedman D. J., Treffry A., Candy J. M., Taylor G. A. A., Morris C. M., Bloxham C. A., Perry R. H., Edwardson J. A., and Harrison P. M. (1992) Iron and aluminum in relation to brain ferritin in normal individuals and Alzheimer's disease and chronic renal dialysis patients.Biochem. J. 287, 509–514.
Evans P. H., Klinowski J., and Vano E. (1991) Cephaloconiosis: a free radical perspective on the proposed particulate-induced etiopathogenesis of Alzheimer's dementia and related disorders.Med. Hypotheses 34, 209–219.
Evans P. H., Peterhans E., Burge T., and Klinowski J. (1992) Aluminosilicate-induced free radical generation by murine brain glial cells in vitro: potential significance in the aetiopathogenesis of Alzheimer's dementia.Dementia 3, 1–6.
Fleming J. T., and Joshi J. G. (1991) Ferritin: the role of aluminum in ferritin function.Neurobiol. Aging 12, 413–418.
Fraga C. G., Oteiza P. I., Golub M. S., Gershwin M. E., and Keen C. L. (1990) Effects of aluminum on brain lipid peroxidation.Toxicol. Lett. 51, 312–219.
Garrel C., Lafond J. L., Guiraud P., Faure P., and Favier A. (1994) Induction of production of nitric oxide in microglial cells by insoluble form of aluminum.Ann. NY Acad. Sci. 738, 455–461.
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.
Gutteridge J. M. C., Quinlan G. J., Clark I., and Halliwell B. (1985) Aluminum salts accelerate peroxidation of membrane lipids stimulated by irons salts.Biochim. Biophys. Acta 835, 441–447.
Halliwell, B. (1989) Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action?Free Rad. Biol. Med. 7, 645–651.
Hensley K., Carney J. M., Mattsom M. P., Aksenova M., Harris M., Wu J. F., Floyd R. A., and Butterfield D. A. (1994) A model for beta-amyloid aggregation and neurotoxicity based on a free radical generation by the peptide: relevance to Alzheimer disease.Proc. Nat. Acad. Sci. 91, 3270–3274.
Hirsch E. C., Brandel J-P., Galle P., and Javoy-Agid F. (1991) Iron and aluminum increase in the substantia nigra of patients with Parkinson's disease: an X-ray microanalysis.J. Neurochem. 56, 46–51.
Kruck T. P. A., Fisher E. A., and McLachlan D. R. C. (1993) Suppression of deferoxamine mesylate side effects by co-administration of isoniazid in a patient with Alzheimer's disease subject to aluminum removal by ion specific chelation.Clin. Pharm. Ther. 48, 439–446.
Kukiella E. and Cederbaum A. E. (1994) Ferritin stimulation of hydroxyl radical production by rat liver nuclei.Arch. Biochem. Biophys. 308, 70–88.
LeBel C. P. and Bondy S. C. (1990) Sensitive and rapid quantitation of oxygen reactive species formation in rat synaptosomes.Neurochem. Int. 17, 435–440.
Mantyh P. W., Ghilardi J. R., Rogers S., DeMaster E., Allen C. J., Stimson E. R., and Maggio J. E. (1993) Aluminum, iron and zinc ions promote aggregation of physiological concentrations of β-amyloid peptide.J. Neurochem. 61, 1171–1174.
McLachlan D. R. C., Lukiw W. J., and Kruck T. P. A. (1989) New evidence for an active role of aluminum in Alzheimer's disease.Can. J. Neurol. Sci. 16, 490–497.
Oteiza P. I. (1994) A mechanism for the stimulatory effect of aluminum on iron induced lipid peroxidation.Arch. Biochem. Biophys. 308, 374–379.
Oteiza P. I., Fraga C. G., and Keen C. L. (1993) Aluminum has both oxidant and antioxidant effects in mouse brain membranes.Arch. Biochem. Biophys 300, 517–521.
Pappolla M. A., Omar R. A., Kim K. S., and Robakis N. K. (1992) Immunohistochemical evidence of antioxidant stress in Alzheimer's disease.Am. J. Pathol. 140, 621–628.
Perl D. P., Gajdusek D. C., Garruto R. M., Yanagihara R. T., and Gibbs C. J. (1982) Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonian-dementia of Guam.Science 217, 1053–1055.
Roskams A. J. and Connor J. R. (1990) Aluminum access to the brain: a role for transferrin and its receptor.Proc. Natl. Acad. Sci. USA 87, 9024–9027.
Shigematsu K. and McGeer P. L. (1992) Accumulation of amyloid precursor protein in damaged neuronal processes and microglia following intracerebral administration of aluminum salts.Brain Res. 593, 117–123.
Smith C. D., Carney J. M., Starke-Reed P. E., Oliver C. N., Stadtman E. R., and Floyd R. A. (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and Alzheimer's disease.Proc. Natl. Acad. Sci. USA 88, 10540–10543.
Subbarao K. V., Richardson J. S., and Ang L. C. (1990) Autopsy samples of Alzheimer's cortex show increased peroxidation in vitro.J. Neurochem. 55, 342–345.
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Bondy, S.C., Kirstein, S. The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum. Molecular and Chemical Neuropathology 27, 185–194 (1996). https://doi.org/10.1007/BF02815093
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DOI: https://doi.org/10.1007/BF02815093