Comparative aluminium mobilizing actions of deferoxamine and four 3-hydroxypyrid-4-ones in aluminium-loaded rats

The efficacy of the Al chelating drugs deferoxamine (DFO) a nd the hydoxypy ridones (HPs): 1,2-dimethyl-3-hydroxypyrid-4-one (L1), 1-[3-hydroxy-2-methy l-4-oxopyridyl]-2-ethanesulfonic acid (L6), 1-benzyl-(4-carboxylic acid)-3- hydroxy-2-methyl-4-oxopyridine (Bzcal) and 1-(p-methylbenzyl)-2-ethyl-3-hyd roxypyrid-4-one (MeBzEM) in increasing Al excretion and reducing tissue Al accumulation has been compared in adult male rats which had previously rece ived Al nitrate nonahydrate i.p. at 0.16 mmol/kg per day for 2 months. At t he end of this period, DFO was injected s.c. and the HPs were given by gava ge at 0.89 mmol/kg per day for five consecutive days. Total urines were col lected 24 h after each chelalor administration. Following chelation treatme nt animals were killed and samples of brain, bone, liver, kidney, and splee n were collected. DFO administration increased to about 4 x the cumulative urinary Al elimination for 5 days, while the excretion of Al into urine cau sed by Bzcal, L1, and MeBzEM administration was about twice that of the con trol group. On the other hand, treatment with Bzcal, DFO, and MeBzEM for 5 days significantly reduced the Al levels in bone by 31, 33, and 29%, and th e Al concentrations in brain by 46, 69, and 71%, respectively. These result s suggest that oral administrations of MeBzEM and Bzcal can be potential al ternatives to parenteral administration of DFO in Al removal. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.