Interaction with protein SH groups could be involved in adriamycin cardiotoxicity

The use of the antineoplastic agent adriamycin is limited by its cardiotoxicity. The mechanism of cardiotoxicity has been investigated through the study of adriamycin effects on a number of heart enzymes. Adriamycin inhibited the activity of NADP-isocitrate dehydrogenase, malic enzyme, and 6-phosphogluconate dehydrogenase, three enzymes that have in common the presence of reactive SH groups involved in activity. Adriamycin action was prevented by the presence of proteins or dithioerythrol and mimicked by dithiobis dinitrobenzoate. It is suggested that adriamycin effects are due to interaction with enzyme SH groups by a product of adriamycin metabolism.