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Lipid peroxide levels were measured in mouse tissues to study their relation to the cardiotoxicity of anthracyclines. The effects of tetrahydropyranyladriamycin (THP-ADR) and 4'-epiadriamycin (4'-epi-ADR), which are less cardiotoxic than adriamycin (ADR), were examined. Neither THP-ADR nor 4'-epi-ADR increased the lipid peroxide levels in the heart, however, both increased reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lipid peroxidation in mouse liver and lung microsomes, to the same degree as ADR. Therefore, the results obtained in vitro were not the same as those obtained in vivo. Of all of the anthracyclines tested, only THP-ADR increased the lipid peroxide levels in the lung. Thus, THP-ADR may be pulmotoxic. Differences in the activities of glutathione peroxidase and glutathione S-transferase reflected the differences in lipid peroxide levels.

Effect of Tetrahydropyranyladriamycin(THP-ADR) and 4'-Epiadriamycin(4'-Epi-ADR) on Lipid Peroxide Levels in Mice.