Deferoxamine toxicity in hepatoma and primary rat cortical brain cultures

Deferoxamine is commonly used for treatment of iron intoxication. Because t he usual dose is unable to chelate sufficient iron before severe injury occ urs, "high-dose" deferoxamine treatment has been proposed. However, several authors have reported severe toxicity after deferoxamine therapy. Although the hemodynamic effects are well described, the cellular toxicity of defer oxamine is unknown. Accordingly, we investigated the cellular toxicity of d eferoxamine using in vitro techniques in two cell lines. Brain cells were h arvested from fetal rats and cultured for 14-21 days before deferoxamine ex posure. Using similar techniques, rat hepatoma cells were grown until confl uent. Deferoxamine was added to the cultures to achieve final concentration s of 200-800 mug/ml, corresponding to in vivo infusion rates of 15-60 mg/kg /h. Deferoxamine was removed after 3 or 6 days by changing the medium. Subt oxic FeCl3 (500 mg/dl) was concurrently added to identical cultures to dete rmine if deferoxamine potentiated iron toxicity. Cell viability was measure d by a colorimetric assay. The addition of deferoxamine (0.2, 0.4, 0.8 mg/m l) significantly decreased cell viability in both cell groups. The effect o f deferoxamine on primary cortical brain cultures was similar for the three concentrations used, and was similar when examined either 72 h or 6 days l ater. In contrast, hepatoma cell cultures evidenced a dose-dependent cell l oss that increased with the length of exposure. The addition of subtoxic am ounts of FeCl3 (500 mug/dl) in the presence of deferoxamine was protective in all cultures, and abolished deferoxamine-induced cell loss. Interestingl y, the addition of serum albumin significantly reduced the amount of iron p resent in cells, suggesting its potential use to treat iron toxicity. These results suggest that deferoxamine, in the absence of iron, is toxic to cor tical brain and hepatoma cells in vitro.