EFFECT OF DESFERRIOXAMINE ON THE HEPATOTOXICITY OF ADRIAMYCIN IN NORMAL MICE

The effect of the iron chelator, desferrioxamine (DFO) upon the hepato toxic effects associated with the use of adriamycin as a cytotoxic age nt were evaluated in normal albino mice. Hepatocellular toxicity was a ssessed by measuring serum aspartate transaminase (SGOT), serum alanin e transaminase (SGPT) and serum alkaline phosphatase (ALP) activity. I n addition, glucose-6-phosphatase (G-6-PTase) activity, nucleic acids, calcium, magnesium, and iron levels in liver tissue were also measure d. Adriamycin treatment (2 mg/kg i.p.), administered every other day f or a total of 5 doses produced a 2.5-fold increase in SGOT and SGPT, w hile ALP activity showed a 30% increase in comparison to normal, untre ated controls. However, hepatic G-6-PTase activity showed a significan t decrease after the adriamycin treatment regimen. The calcium and iro n content of liver showed also a marked decrease, while magnesium leve ls were increased two-fold after treatment with adriamycin. In the pre sence of the iron chelator, DFO (100 mg/kg i.p., administered every ot her day for 5 doses), adriamycin treatment did not result in any signi ficant changes in SGOT, SGPT, ALP, or hepatic G-6-PTase activity. Hist opathological examination of mouse liver showed diffuse ballooning deg eneration of liver cells with perivascular cellular infiltration after adriamycin treatment. In the presence of DFO, only focal cellular deg enerative and minimal fatty changes were observed. The observed hepato cellular damage is believed to be a result of the lipid peroxidation i nduced by adriamycin. The role of DFO in preventing lipid peroxidation has been discussed. This study provides evidence that DFO may be usef ul for prevention of the lipid peroxidation and hepatocellular damage induced by adriamycin.