The influence of doxorubicin and 4'-epi-doxorubicin on lipid peroxidation in mouse heart, lungs and liver. Part II.

Influence of doxorubicin (DOX) and its less cardiotoxic analog 4'-epi-doxorubicin (EPI) on the peroxidation of cellular components was evaluated in vivo. Previous experimental work performed at our laboratory indicates that DOX, but not EPI, induces a marked increase in conjugated dienes formation (CD) in mice hearts exposed to a single intravenous dose (30 mg/kg) of that drug. Therefore, in the present study lipid peroxidation after treatment with these anthracyclines, was evaluated and compared in vivo by measuring the content of malondialdehyde (MDA) in heart, liver and lungs of Balb/c mice over 48-h period at various time-points: 5, 24 and 48 h after a single intravenous injection of either DOX or EPI. A statistically significant increased formation of MDA was found after both DOX and EPI in mice heart, lung and liver homogenates. DOX caused a relatively higher increase in MDA formation than did EPI. The results obtained in this study indicate that both DOX and EPI induce peroxidation of tissue components in vivo as shown by the increase in the formation of MDA. However, only DOX induces significant increase in lipid peroxidation in cardiac muscle, as assessed by the formation of CD. The results also suggest that peroxidation of other tissue components may be responsible for anthracycline-induced cardiotoxicity.