Anthracycline-induced oxygen consumption and oxidative damage in rat liver microsomes are not necessarily coupled. A study with 8 structurally related anthracyclines.

The stimulative effect of 8 anthracyclines (the parent compounds daunorubicin and doxorubicin and 6 structurally closely related anthracyclines) on the production of thiobarbituric acid (TBA)-reactive material was investigated in liver microsomes. Except for daunorubicinone and doxorubicinone, all derivatives stimulated NADPH-dependent production of TBA-reactive material. Doxorubicinone had no effect, daunorubicinone inhibited TBA-reactivity at concentrations up to 50 microM. However, the latter two compounds stimulated oxygen consumption in the presence of EDTA to a degree comparable to that induced by the parent compounds. Since the oxygen uptake under these circumstances represents redox cycling of the drugs, apparently redox cycling and production of TBA-reactive material were not coupled for these compounds. Spectral measurements showed no decisive role for interaction with free iron (Fe3+) ions in the non-coupling of redox cycling and production of TBA reactive material. Evidence for a role of bound iron ions was not obtained. It is discussed that for the aglycones oxygen consumption and production of TBA reactive material might be non-coupled through their different interaction with microsomal RNA.