Age-Related differences on aluminium mobilization by chelating agents in aluminium-loaded uraemic rats.
The efficacy of deferoxamine, deferiprone, and a combination of these chelating agents in the mobilization and promotion of aluminium (Al) excretion was compared in two age groups of uraemic rats which had previously received Al nitrate nonahydrate intraperitoneally in a daily dose of 45 mg/kg for 5 weeks. At the end of the period of Al exposure, Al-loaded rats of each age (young and adult) group were given one of the following treatments for 5 days: 0.90 mmol/kg/ day of deferoxamine (subcutaneously), 0.90 mmol/kg/day of deferiprone (orally), and 0.45 mmol/kg/day of deferoxamine (subcutaneously) plus 0.45 mmol/kg/day of deferiprone (orally). Control rats were given 0.9% saline (subcutaneously) and deionized water (orally). Total urines were collected 24 hr after each chelator administration. Although young rats treated with deferoxamine, deferiprone, or deferoxamine plus deferiprone showed significant increases in the total amount of Al excreted into urine during 5 consecutive days, the effect of combined administration of deferoxamine and deferiprone was lower than that caused by deferoxamine or deferiprone only. On the other hand, after administration of deferoxamine and deferiprone, a significant reduction of Al was noted only in the liver of young rats, while no significant effects of the chelators were seen in any of the examined tissues of adult animals. The results of the current study show that a combined therapy with deferoxamine and deferiprone (at half-doses of each drug) can also be effective in mobilizing Al from the body of Al-loaded uraemic rats.
Esparza
J L
JL
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, Reus, Spain.
Gómez
M
M
Domingo
J L
JL
del Castillo
D
D
Hernández
M
M
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism*; D000535:Aluminum / Q000652:urine*; D017607:Aluminum Compounds / Q000633:toxicity*; D000818:Animals; D000871:Anthelmintics / Q000633:toxicity*; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D007279:Injections, Subcutaneous; D008297:Male; D009566:Nitrates / Q000633:toxicity*; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000188:drug therapy* / Q000378:metabolism
D017607:Aluminum Compounds; D000871:Anthelmintics; D002614:Chelating Agents; D009566:Nitrates; D011728:Pyridones; D000077543:Deferiprone; D000535:Aluminum; C050609:aluminum nitrate; D003676:Deferoxamine