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Research Article| Volume 42, ISSUE 10, P1296-1300, October 1993

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Aluminum accumulation and neurotoxicity in Swiss-Webster mice after long-term dietary exposure to aluminum and citrate

  • Patricia I. Oteiza
    Footnotes
    Affiliations
    Instituto de Quimica y Fisicoquimica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina

    the Department of Nutrition, University of California, Davis, CA, USA.

    the Department of Internal Medicine, University of California, Davis, CA, USA.
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  • Carl L. Keen
    Correspondence
    Address reprint requests to Carl L. Keen, PhD, Department of Nutrition, University of California, Davis, CA 95616-8669.
    Affiliations
    Instituto de Quimica y Fisicoquimica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina

    the Department of Nutrition, University of California, Davis, CA, USA.

    the Department of Internal Medicine, University of California, Davis, CA, USA.
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  • Bin Han
    Affiliations
    Instituto de Quimica y Fisicoquimica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina

    the Department of Nutrition, University of California, Davis, CA, USA.

    the Department of Internal Medicine, University of California, Davis, CA, USA.
    Search for articles by this author
  • Mari S. Golub
    Affiliations
    Instituto de Quimica y Fisicoquimica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina

    the Department of Nutrition, University of California, Davis, CA, USA.

    the Department of Internal Medicine, University of California, Davis, CA, USA.
    Search for articles by this author
  • Author Footnotes
    1 Present address: P.I.O., Instituto de Quimica y Fisicoquimica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Junin 954, 1113-Buenos Aires, Argentina.
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      Abstract

      The present study was performed to determine aluminum uptake, retention, and neurotoxic effects in the presence of dietary citrate. Six-week-old female Swiss-Webster mice were fed semipurified diets containing 3.5% sodium citrate and either 3 μg Al/g diet (3 Al) or 1,000 μg Al/g diet (1,000 Al) as AlCl3. After 5 to 7 weeks of feeding these diets, changes in behavior were assessed using the National Institute of Environmental Health Sciences Neurobehavioral Test Battery. Liver and bone Al concentrations in the 1,000 Al group were higher than in the 3 Al group at both the 5- and 7-week time points. Spinal cord Al concentrations in the 1,000 Al group were 200% higher at 5 weeks (P < .01) than in controls, and brain nuclear fraction Al concentrations in the 1,000 Al group were 150% higher at 5 and 7 weeks (P < .01) than in the 3 Al group. The Neurobehavioral Test Battery showed lower grip strength and greater startle responsiveness in the 1,000 Al group compared with the 3 Al group at both the 5- and 7-week time points. Based on reports that Al can act as a pro-oxidant, we examined Al-induced brain lipid and protein oxidative damage; neither was evident in the Al-intoxicated mice. In summary, feeding of Al and citrate to mice resulted in Al accumulation in the central nervous system, and this accumulation was associated with overt signs of neurotoxicity. Brain protein and lipid oxidative damage was not associated with early manifestation of Al toxicity.
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