Aluminum chelation by 3-hydroxypyridin-4-ones in the rat demonstrated by microdialysis.
The ability and site of the metal-chelating 3-hydroxypyridin-4-ones (HPs) to mobilize aluminum (Al) was assessed in Al-loaded rats using microdialysis. Four HPs with greatly varying lipophilicity were studied. One week after Al loading, microdialysis probes were implanted in the liver, a jugular vein, and the frontal cortex. An HP was given iv followed by continuous microdialysis for 5 h. Al concentrations in dialysates from the liver increased rapidly and were consistently greater than from blood, suggesting that liver was a primary site of Al chelation. Brain dialysate Al concentrations remained low, suggesting little Al chelation in the brain and little distribution of the Al HP complex into the brain. Al concentrations were determined in the main organs/tissues of a separate group of Al-loaded rats, and the percentage of the total Al body burden in each organ/tissue was calculated. The skeletal system and liver had 57 and 28% of the Al body burden, consistent with the liver as a primary site of Al chelation. The HPs chelate extravascular Al and have been shown by others to be orally active. They warrant further investigation as Al chelators.
Yokel
R A
RA
College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
D000535:Aluminum / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001822:Body Burden; D002614:Chelating Agents / Q000737:chemistry*; D008297:Male; D017551:Microdialysis; D011728:Pyridones / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002614:Chelating Agents; D011728:Pyridones; D000535:Aluminum