Aluminum mobilization by desferrioxamine assessed by microdialysis of the blood, liver and brain.
Aluminum (Al) mobilization by i.v. desferrioxamine (DFO) into blood and into brain and liver extracellular space was followed in the Al-loaded rat using microdialysis probes. Dialyzable extracellular liver Al peaked at an estimated 1360 microgram/l whereas dialyzable blood and extracellular brain Al peaked at 860 and 155-175 microgram/l, respectively. Estimated Al concentrations were derived from dialysate Al from microdialysis probes which was corrected for probe efficiency. Liver Al after DFO was generally greater than blood Al. Both declined over time. The rapid increase in extracellular liver Al above blood Al suggests the ability of DFO to rapidly distribute out of the vascular compartment to mobilize Al from hepatocytes. Presumably an Al-DFO complex was formed and released into blood, from which it was eliminated. Extracellular brain Al and DFO was less than blood Al and did not decline during 5 h. After an i.v. Al-DFO injection to non-Al-loaded rats, blood Al was greater than liver much greater than brain Al, suggesting Al-DFO diffusion down a concentration gradient and demonstrating the ability of Al-DFO to permeate vascular membranes and the blood-brain barrier. The lack of decline of brain extracellular Al after DFO was presumably due to its inability to diffuse into the blood against the concentration gradient. The DFO-induced mobilization of Al in the brain may explain the reports of sudden onset or worsening of encephalopathy associated with DFO treatment of Al-loaded humans.
Yokel
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College of Pharmacy and Graduate Center for Toxicology, University of Kentucky, Lexington 40536-0082.
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Ungerstedt
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D000535:Aluminum / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D015913:Chelation Therapy; D003676:Deferoxamine / Q000627:therapeutic use*; D003956:Dialysis; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013054:Spectrophotometry, Atomic
D000535:Aluminum; D003676:Deferoxamine