Chelation therapy in aluminum-loaded rats: influence of age.
The influence of age at which aluminum (Al) exposure was initiated on the efficacy of chelation therapy in mobilizing Al was investigated in two groups of male rats exposed to this element at two different stages of the life cycle. Young (21 days old) and old (18 months) rats were exposed to 0 and 50 mg Al/kg/day administered as Al nitrate in drinking water for a preliminary period of 14 days followed by a period of 100 days, in which Al-exposed animals received 100 mg Al/kg/day. At the end of the period of exposure, Al-loaded rats in each age group were given one of the following treatments: s.c. deferoxamine (DFO), oral 1,2-dimethyl-3-hydroxypyrid-4-one (L1) and 1-(p-methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one (MeBzEM) at doses of 0.89 mmol/kg/day for 5 consecutive days. Another group of Al-exposed rats received a concurrent administration of s.c. DFO and oral L1 both at 0.45 mmol/kg/day. During chelation therapy urines were collected daily. Control groups included rats exposed and unexposed to Al. Oral administration of L1 was the most effective treatment in enhancing urinary Al excretion in both age groups of Al-loaded rats. This beneficial effect was similar for old and young animals. Concurrent administration of DFO and L1 had no advantages over the use of either single agent, while MeBzEM was not effective in mobilizing Al from Al-exposed rats.
Gómez
M
M
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, Reus, Spain.
Esparza
J L
JL
Domingo
J L
JL
Singh
P K
PK
Jones
M M
MM
D000375:Aging / Q000378:metabolism*; D000535:Aluminum / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D015913:Chelation Therapy; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
C121879:1-(p-methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one; D000931:Antidotes; D002614:Chelating Agents; D011725:Pyridines; D011728:Pyridones; D000077543:Deferiprone; D000535:Aluminum; D003676:Deferoxamine