Adriamycin-induced oxidation of myoglobin

Lawrence C. Trost, Kendall B Wallace

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Numerous mechanisms have been invoked to explain the cardiotoxicity of Adriamycin, most of which share a requirement for iron. Adriamycin is chemically reactive with iron loosely associated with subcellular membranes as well as with ferritin and the heme iron of hemoglobin. The present investigation examined whether Adriamycin also reacts with myoglobin, an abundant source of iron in cardiac muscle. Adriamycin caused a 4-fold stimulation of the autoxidation of oxymyoglobin to metmyoglobin. Hydrogen peroxide is an obligatory intermediate as catalase completely inhibited the reaction. Superoxide dismutase, however, was without effect. This interaction of Adriamycin with myoglobin may impose significant restrictions on oxygen storage and delivery in vivo. In light of the abundance of myoglobin and the deficiency of catalase in the heart, this interaction with myoglobin may be an important determinant of the cardioselective toxicity of Adriamycin.

Original languageEnglish (US)
Pages (from-to)30-37
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume204
Issue number1
DOIs
StatePublished - Oct 15 1994

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