Entry, half-life, and desferrioxamine-accelerated clearance of brain aluminum after a single (26)Al exposure.
The objectives of our study were to estimate the percentage of aluminum (Al) that enters the brain, the half-life of brain Al, and the ability of an Al chelator to reduce brain Al. Rats received an iv infusion of Al transferrin, the primary Al species in plasma, or Al citrate, the predominant small molecular weight Al species in plasma. The infusion contained approximately 0.2-0.3 nCi (0.4-0.6 nmol) (26)Al, enabling the study of Al distribution into and retention by the brain at physiological Al concentrations. Some Al transferrin-infused rats received ip injections of the Al chelator desferrioxamine (DFO), 0.15 mmol/kg, three times weekly. The others received saline injections. The rats were euthanized from 4 hr to 4 days (Al citrate) or 256 days (Al transferrin) later. Brain (26)Al was determined by accelerator mass spectrometry. Peak brain (26)Al concentration was approximately 0.005% of the (26)Al dose in each gram of brain, irrespective of Al species administered. In the absence of DFO treatments, brain (26)Al concentration decreased with a half-life of approximately 150 days. The brain Al half-life in the DFO-treated rats was approximately 55 days. The results show a small fraction of Al in blood enters the brain, where it persists for a long time. The ability of repeated DFO treatments to modestly accelerate the reduction of brain Al is consistent with the necessity of prolonged DFO therapy to significantly reduce Al-induced dialysis encephalopathy.
Yokel
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College of Pharmacy and Graduate Center for Toxicology, University of Kentucky Medical Center, Lexington, Kentucky 40536-0082, USA. ryokel1@uky.edu
Rhineheimer
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Sharma
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Elmore
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McNamara
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PJ
D000535:Aluminum / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011868:Radioisotopes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D014168:Transferrin / Q000008:administration & dosage / Q000493:pharmacokinetics
D002614:Chelating Agents; D011868:Radioisotopes; D014168:Transferrin; D000535:Aluminum; D003676:Deferoxamine