Deferoxamine toxicity in hepatoma and primary rat cortical brain cultures.
Deferoxamine is commonly used for treatment of iron intoxication. Because the usual dose is unable to chelate sufficient iron before severe injury occurs, "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 deferoxamine is unknown. Accordingly, we investigated the cellular toxicity of deferoxamine using in vitro techniques in two cell lines. Brain cells were harvested from fetal rats and cultured for 14-21 days before deferoxamine exposure. Using similar techniques, rat hepatoma cells were grown until confluent. Deferoxamine was added to the cultures to achieve final concentrations of 200-800 microg/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. Subtoxic FeCl3 (500 mg/dl) was concurrently added to identical cultures to determine if deferoxamine potentiated iron toxicity. Cell viability was measured by a colorimetric assay. The addition of deferoxamine (0.2, 0.4, 0.8 mg/ml) significantly decreased cell viability in both cell groups. The effect of deferoxamine on primary cortical brain cultures was similar for the three concentrations used, and was similar when examined either 72 h or 6 days later. In contrast, hepatoma cell cultures evidenced a dose- dependent cell loss that increased with the length of exposure. The addition ofsubtoxic amounts of FeCl3 (500 microg/dl) in the presence of deferoxamine was protective in all cultures, and abolished deferoxamine-induced cell loss. Interestingly, the addition of serum albumin significantly reduced the amount of iron present in cells, suggesting its potential use to treat iron toxicity. These results suggest that deferoxamine, in the absence of iron, is toxic to cortical brain and hepatoma cells in vitro.
Christensen
D W
DW
Department of Pediatrics, Loma Linda University School of Medicine, California 92350, USA.
Kisling
R
R
Thompson
J
J
Kirby
M A
MA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D018929:Cell Culture Techniques; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D003676:Deferoxamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000166:cytology; D007501:Iron / Q000633:toxicity; D007502:Iron Chelating Agents / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007502:Iron Chelating Agents; D012709:Serum Albumin; D007501:Iron; D003676:Deferoxamine