Chelation of aluminium by combining DFO and L1 in rats

The hypothesis that two known chelators 1,2-dimethyl-3-hydroxypyrid-4-one ( L1) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing aluminium from the body was tested in a new acute rat model. Five-week old female rats received chelators: L1 (p.o. ), DFO (i.p.) or L1 + DFO as 100 or 200 mg/kg dose half an hour after a sin gle i.p. administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminium concentration and urinary aluminium and iron excretions wer e determined by electrothermal or flame atomic absorption spectrometry. Bot h chelators were effective only at the higher dose level. While DFO was mor e effective than L1 in enhancing urinary aluminium excretion, L1 was more e ffective than DFO in enhancing urinary iron excretion. In the combined trea tment group L1 did not increase the DFO effect on aluminium and DFO did not increase the effect of L1 on iron elimination. However, in this group a si multaneous increase in both aluminium and iron elimination was observed. Ou r results support the usefulness of this animal model for preliminary in vi vo testing of aluminium chelators. Urinary values were more useful because of the high variability of serum results. Result of combined chelators trea tment should be confirmed in a different experimental model before extrapol ation to other systems. This testing procedure of course does not provide a ll the relevant answers for evaluating the efficiency of chelating agents i n aluminium toxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights res erved.