Comparative effects of deferasirox and deferiprone in the treatment of copper intoxication in rats

Abstract

The hypothesis that two known chelators deferiprone (L1) and deferasirox (DFS) might be more efficient as combined treatment than monotherapies in the mobilization of copper was tested in copper-exposed rats. Male Wistar rats were exposed to 70 mg/kg body weight copper (II) chloride in drinking water for 42 d, followed by treatment with DFS (60 mg/kg body weight, oral, once daily), L1 (60 mg/kg body weight, oral, once daily) either alone or in combination DFS + L1 (30 mg/kg body weight, oral, once daily), for 10 consecutive days. After chelation therapy, these rats were anesthetized by ether vapor and immobilized by cervical dislocation. Then their heart, kidneys, liver and intestine were sampled for determination of copper, iron and zinc concentration with an atomic absorption spectrophotometer. The treatment with DFS and L1 appreciably decreased the depletion of endogenous copper, but the combined treatments were more efficient than the individuals in restoring the tissue copper levels. Furthermore, iron and zinc concentration after chelation therapy significantly decreased, thus consumption of iron and zinc tablet is recommended to return iron and zinc level to its normal state. Our results support the usefulness of this animal model for preliminary in vivo testing of copper chelators. The result of combined chelators treatment should be confirmed in a different experimental model before extrapolation to other systems.