Removal of vanadium by combining desferrioxamine and deferiprone chelators in rats

Abstract

Investigations were conducted to evaluate the ability of two chelators, desferrioxamine (DFO), and deferiprone (1,2-dimethy1-3-hydroxypyride-4-one, L 1 ), for the excretion of vanadium after a period of administration of vanadium salts in 6-week-old male Wistar rats. Immediately after 60 days of vanadium administration, the rats received chelators (L 1 , DFO or L 1 ? DFO) for a period of 1 week. Chelators were given orally (L 1 ), intraperitoneally (DFO), or both to different groups of rats at two different dosage levels. After chelation therapy, animals were sacrificed by exsanguination from abdominal aorta. Blood, kidney, liver, and heart samples were collected and prepared for determination of vanadium and iron concentrations by graphite furnace and flame atomic absorption spectroscopy (GF AAS, and F AAS) methods, respectively. These chelators significantly enhanced the urinary and biliary excretion of vanadium and restored the altered levels of iron. Furthermore, the hypothesis that these two known chelators might be more effective in removing vanadium from the body as a combined treatment than as monotherapy also was tested in this study. Although there is no significant difference between these two chelators in reducing the vanadium concentration, combination therapy (L 1 ? DFO) may cause higher efficacy and lower toxicity compared with monotherapies. Collectively, the results indicate that the designed procedure might be useful for preliminary in vivo testing of the efficiency of a chelating agent. However, our findings regarding the efficacy of combination therapy should be confirmed in more experiments. This preliminary study does not provide all answers to the magnitude of the efficiency of chelating agents in vanadium toxicity, and thus, further research is warranted.

Chelation of cadmium by combining deferasirox and deferiprone in rats

“…This kind of therapy by combining two chelators is based on the assumption that various chelating agent mobilize toxic element from different tissue compartments and therefore better results are expected (Flora et al, 1995). Results of this kind of combined chelation therapy has been confirmed by Fatemi et al (Amiri et al, 2007;Fatemi et al, 2007Fatemi et al, , 2009Tubafard et al, 2010;Tubafard and Fatemi, 2008). The aim of this study was to test the chelation potency of deferasirox and L 1 in combination, given to animals after Cd loading.…”

Clinical evaluation of Deferasirox for removal of cadmium ions in rat

“…It is obvious that the cadmium concentration after chelation therapy was significantly decreased (P < 0.05). To investigate the effect of passing time in removing cadmium from the body spontaneously, one group was treated without chelation therapy (Fatemi et al 2007(Fatemi et al , 2009Tubafard and Fatemi 2008;Tubafard et al 2010). Elimination of cadmium by the biological system in the groups without the chelation therapy is not noticeable (Table 3).…”

“…Clinical evaluations of some chelators for removal of toxic metal ions in rats have been previously reported by (Fatemi et al 2007(Fatemi et al , 2009Tubafard and Fatemi 2008;Tubafard et al 2010). Chelation therapy is one of the most effective ways to remove toxic elements from the biological system.…”

“…In view of these considerations, there is a great need for the development of an alternative orally effective chelating drug. Recently, many candidate compounds have been screened in animal models (Scott and Orvig 2009;Fatemi et al 2007Fatemi et al , 2009Tubafard and Fatemi 2008;Tubafard et al 2010). Many of them have poor solubility, numerous side effects and a high production cost.…”

The Effect of Mercury in Iron Metabolism in Rats

“…and to remove undesirable metal ions [4,5,[8][9][10][11]. Recently in chelation therapy, many candidate compounds have been screened in animal models [11].…”