EFFECT OF DESFERRIOXAMINE ON THE HEPATOTOXICITY OF ADRIAMYCIN IN NORMAL MICE

The effect of the iron chelator, desferrioxamine (DFO) upon the hepatotoxic effects associated with the use of adriamycin as a cytotoxic agent were evaluated in normal albino mice. Hepatocellular toxicity was assessed by measuring serum aspartate transaminase (SGOT), serum alanine transaminase (SGPT) and serum alkaline phosphatase (ALP) activity. In addition, glucose-6-phosphatase (G-6-PTase) activity, nucleic acids, calcium, magnesium, and iron levels in liver tissue were also measured. Adriamycin treatment (2 mg/kg i.p.), administered every other day for a total of 5 doses produced a 2.5-fold increase in SGOT and SGPT, while ALP activity showed a 30% increase in comparison to normal, untreated controls. However, hepatic G-6-PTase activity showed a significant decrease after the adriamycin treatment regimen. The calcium and iron content of liver showed also a marked decrease, while magnesium levels were increased two-fold after treatment with adriamycin. In the presence of the iron chelator, DFO (100 mg/kg i.p., administered every other day for 5 doses), adriamycin treatment did not result in any significant changes in SGOT, SGPT, ALP, or hepatic G-6-PTase activity. Histopathological examination of mouse liver showed diffuse ballooning degeneration of liver cells with perivascular cellular infiltration after adriamycin treatment. In the presence of DFO, only focal cellular degenerative and minimal fatty changes were observed. The observed hepatocellular damage is believed to be a result of the lipid peroxidation induced by adriamycin. The role of DFO in preventing lipid peroxidation has been discussed. This study provides evidence that DFO may be useful for prevention of the lipid peroxidation and hepatocellular damage induced by adriamycin.