Inhibition of adriamycin-stimulated microsomal lipid peroxidation by mitoxantrone and ametantrone,two new anthracenedione antineoplastic agents |
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Authors: | Evan D Kharasch Raymond F Novak |
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Institution: | 1. Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611 USA;2. Northwestern University Dental School, Chicago, Illinois 60611 USA |
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Abstract: | Ametantrone and mitoxantrone, two new anthracenedione antineoplastic agents, produced a concentration-dependent inhibition of hepatic microsomal lipid peroxidation. Malondialdehyde production was diminished from 10.6 nmoles/mg/60 min to 3.3 and 5.4 nmoles/mg/60 min, in the presence of 100 μM mitoxantrone and ametantrone, respectively. Under similar conditions, Adriamycin stimulated lipid peroxidation over twofold. In addition, both mitoxantrone and ametantrone inhibited Adriamycin-stimulated lipid peroxidation, with 50% inhibition occurring at concentrations of 4 and 6 μM, respectively. Microsomal superoxide production was not significantly inhibited at anthracenedione concentrations which markedly decreased lipid peroxidation, suggesting that inhibition of lipid peroxidation was not the result of inhibition of superoxide generation. These results correlate with the lack of anthracenedione cardiotoxicity and also demonstrate anthracenedione inhibition of lipid peroxidation at micromolar concentrations; an observation with potential therapeutic significance. |
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Keywords: | ADM-Adriamycin MDA-malondialdehyde |
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