Removal of thallium by combining desferrioxamine and deferiprone chelators in rats

Abstract

The hypothesis that two known chelators deferiprone (1,2-dimethy1-3-hydroxypyrid-4-one, L1) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing thallium from the body was tested in rats. Six-week-old male Wistar rats received chelators: L1 (p.o.), DFO (i.p.) or L1 + DFO as 110 or 220 mg/kg dose half an hour after a single i.p. administration of 8 mg Tl/kg body weight in the form of chloride. Serum thallium concentration, urinary thallium and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level, while DFO was more effective than L1 in enhancing urinary thallium 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 thallium and DFO did not increase the effect of L1 on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of thallium 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.

Chelation of cadmium by combining deferasirox and deferiprone in rats

“…A comparison of the results obtained from with and without Chelation therapies indicate that combined (deferasirox þ L 1 ) therapy increases the elimination of Cd effectively, so, removal of Cd is not time dependent at all, also toxicity and side effects of deferasirox and L 1 are very low, therefore after basic preclinical research, they could be recommended for human administration. In comparison to the results obtained by Fatemi et al Amiri et al, 2007;Tubafard and Fatemi, 2008;Fatemi et al, 2009;Tubafard et al, 2010) and our present results, it can be concluded that the two chelators (deferasirox þ L 1 ) are more efficient as combined therapy than single therapy in removing Cd from all tissues.…”

Removal of thallium by deferasirox in rats as biological model

“…Some of thallium toxicity symptoms which appeared during the period of thallium uptake were the appearance of red staining around the eyes, greenish mottling on the liver, weakness and loss of hair and weight. Also our results shown that iron concentration decreased in blood serum, therefore anemia can occur as a result of iron‐poor dietary intake (iron deficiency anemia) (Amiri et al ., 2007; Fatemi et al ., 2007). During thallium administration, its concentration increased in blood serum while iron level decreased.…”

“…Thallium can be released to the environment (Xiao et al ., 2004; Heim et al ., 2002), exposing humans to its noxious effects. For example, it has been reported that thallium can affect several tissues and systems, including the epidermal, gastrointestinal, cardiovascular, reproductive and renal systems (Heim et al ., 2002; Fatemi et al ., 2007; Amiri et al ., 2007). It can also cross the blood–brain barrier, and deposit in the brain, where it causes neurodegeneration, demyelination and the accumulation of end products of lipid oxidation (Galván‐Arzate et al ., 2000).…”

Chelation of chromium(VI) by combining deferasirox and deferiprone in rats

“…This kind of therapy by combining two chelators is based on the assumption that various chelating agents mobilize toxic elements from different tissue compartments and therefore better results are expected (Flora et al 1995). Results of this kind of combined chelation therapy have been confirmed by Amiri et al (2007), Fatemi et al (2007Fatemi et al ( , 2009), Tubafard and Fatemi (2008). The aim of the present research was to test the chelation potency of deferasirox and deferiprone in combination, given to animals after chromium loading.…”

“…These ligands promote the excretion and subsequent depletion of this transition metal in biological systems. Clinical evaluations of some chelators for the removal of toxic metal ions in rats have been previously reported by Amiri et al (2007), Fatemi et al (2007Fatemi et al ( , 2009, Shokooh Saljooghi and Fatemi (2010b), Tubafard and Fatemi (2008). These chelating agents consist of a range of bidentate, tridentate and hexadentate ligands in which two, three or six atoms are able to coordinate, respectively (Clarke and Martell 1992;Gomez et al 1988).…”