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1.
Toxicol Sci ; 64(1): 77-82, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11606803

RESUMO

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.


Assuntos
Alumínio/farmacocinética , Encéfalo/metabolismo , Quelantes/farmacologia , Desferroxamina/farmacologia , Alumínio/administração & dosagem , Alumínio/sangue , Animais , Meia-Vida , Humanos , Masculino , Espectrometria de Massas , Radioisótopos/administração & dosagem , Radioisótopos/metabolismo , Radioisótopos/farmacocinética , Ratos , Transferrina/administração & dosagem , Transferrina/farmacocinética
2.
Toxicology ; 161(1-2): 93-101, 2001 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-11295258

RESUMO

The objectives were to estimate aluminum (Al) oral bioavailability under conditions that model its consumption in drinking water, and to test the hypotheses that stomach contents and co-administration of the major components of hard water affect Al absorption. Rats received intragastric 26Al in the absence and presence of food in the stomach and with or without concomitant calcium (Ca) and magnesium (Mg) at concentrations found in hard drinking water. The use of 26Al enables the study of Al pharmacokinetics at physiological Al concentrations without interference from 27Al in the environment or the subject. 27Al was intravenously administered throughout the study. Repeated blood withdrawal enabled determination of oral 26Al bioavailability from the area under its serum concentrationxtime curve compared to serum 27Al concentration in relation to its infusion rate. Oral Al bioavailability averaged 0.28%. The presence of food in the stomach and Ca and Mg in the water that contained the orally dosed 26Al appeared to delay but not significantly alter the extent of 26Al absorption. The present and published results suggest oral bioavailability of Al from drinking water is very low, about 0.3%. The present results suggest it is independent of stomach contents and water hardness.


Assuntos
Alumínio/farmacocinética , Mucosa Gástrica/metabolismo , Água/química , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Ingestão de Líquidos , Alimentos , Masculino , Ratos , Ratos Endogâmicos F344 , Espectrofotometria Atômica
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