Chelation of aluminium by combining DFO and L1 in rats

• Published in: Toxicology (Amsterdam) 2000-07, Vol.147 (3), p.151-156
• Main Authors: Blanuša, Maja, Prester, Ljerka, Varnai, Veda M., Pavlović, Draško, Kostial, Krista, Jones, Mark M., Singh, Pramod K.
• Format: Article
• Language: English
• Subjects: 1,2 Dimethyl-3-hydroxypyrid-4-one; 1,2-Dimethyl-1-3-hydroxypyrid-4-one; Aluminium; Aluminum - administration & dosage; Aluminum - blood; Aluminum - urine; Animals; Biological and medical sciences; Chelating Agents - pharmacology; Chelation; Chemical and industrial products toxicology. Toxic occupational diseases; Deferiprone; Deferoxamine - pharmacology; Desferrioxamine; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Iron; Iron - blood; Iron - urine; Iron Chelating Agents - pharmacology; Medical sciences; Metals and various inorganic compounds; Pyridones - pharmacology; Rats; Rats, Wistar; Serum; Toxicology; Urine
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(00)00214-6

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 single i.p. administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminium concentration and urinary aluminium and iron excretions were determined by electrothermal or flame atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While DFO was more effective than L1 in enhancing urinary aluminium excretion, L1 was more effective than DFO in enhancing urinary iron excretion. In the combined treatment 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 simultaneous increase in both aluminium and iron elimination was observed. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminium chelators. Urinary values were more useful because of the high variability of serum results. Result of combined chelators treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in aluminium toxicity.