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Adriamycin and derivatives interaction with the mitochondrial membrane: O2 consumption and free radicals formation.

par Pollakis, Georges ;Goormaghtigh, Erik ;Delmelle, Michel;Lion, Yves;Ruysschaert, Jean Marie
Référence Research communications in chemical pathology and pharmacology, 44, 3, page (445-459)
Publication Publié, 1984-06

Article révisé par les pairs

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Résumé :

Adriamycin induces the formation of semiquinone free radicals, O(2) and OH. species, in beef heart intact mitochondria, submitochondrial particles and complex I-III containing proteoliposomes. Free radicals were detected by the use of Electron Spin Resonance (ESR) spectroscopy with the spin trapping method. However, to observe transient oxygen species in intact mitochondria, a flow technique was mandatory. ESR results were compared with oxygen consumption measurements. Since free radicals could be involved in the mechanism of the adriamycin induced cardiotoxicity, it was essential to design new adriamycin derivatives which do not generate radicals. From the study of two adriamycin analogs (N-acetyl-adriamycin and 5-Iminodaunorubicin), it was shown that oxygen radicals formation require both the binding of the drug to the mitochondrial membrane and a quinone function associated with the drug structure. The data reported here might be useful in the synthesis of less cardiotoxic compounds.