Comparative efficacy of several potential treatments for copper mobilization in copper-overloaded rats

D-Penicillamine (DPA) is effective in the treatment of Wilson's disease, wh ereas zinc salts are also used as a therapy for this disorder of copper tra nsport. Recently, it has been shown that the copper chelators 1,4,7,11-tetr aazaundecane tetrahydrochloride (TAUD) and tetraethylenepentamine pentahydr ochloride (TETREN) could be useful for copper mobilization in rats. Because these agents could be potential clinical alternatives to DPA for patients with Wilson's disease who are intolerant to this drug, we examined whether oral administration of TAUD and TETREN could be effective in mobilizing cop per in experimental copper-overloaded rats. The efficacy of a combined admi nistration of zinc and DPA, TAUD, or TETREN was also assessed. Rats were co pper loaded with 0.125% copper acetate in water for 12 wk. After this perio d, DPA, TAUD, and TETREN were administered by gavage at 0.67 mmol/kg/d for 5 d, and zinc was given at 2.5 mg Zn/kg/d. Twelve weeks of copper loading r esulted in a 32-fold increase in total hepatic copper. TETREN was the most effective chelator in increasing the urinary excretion of copper. However, it did not reduce significantly the hepatic copper levels. in turn, combine d administration of zinc and chelating agents significantly reduced the amo unt of copper found in the feces. Although TAUD and TETREN showed a similar or higher efficacy to DPA in mobilizing copper, concurrent treatment of ch elating agents and zinc salts should be discarded according to the current results.