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Cell Biology and Toxicology

, Volume 23, Issue 1, pp 15–25 | Cite as

Adriamycin-induced oxidative mitochondrial cardiotoxicity

  • J. M. Berthiaume
  • K. B. WallaceEmail author
Article

Abstract

The anticancer agent Adriamycin (ADR) has long been recognized to induce a dose-limiting cardiotoxicity. Numerous studies have attempted to characterize and elucidate the mechanism(s) behind its cardiotoxic effect. Despite a wealth of data covering a wide-range of effects mediated by the drug, the definitive mechanism remains a matter of debate. However, there is consensus that this toxicity is related to the induction of reactive oxygen species (ROS). Induction of ROS in the heart by ADR occurs via redox cycling of the drug at complex I of the electron transport chain. Many studies support the theory that mitochondria are a primary target of ADR-induced oxidative stress, both acutely and long-term. This review focuses on the effects of ADR redox cycling on the mitochondrion, which support the hypothesis that these organelles are indeed a major factor in ADR cardiotoxicity. This review has been constructed with particular emphasis on studies utilizing cardiac models with clinically relevant doses or concentrations of ADR in the hope of advancing our understanding of the mechanisms of ADR toxicity. This compilation of current data may reveal valuable insights for the development of therapeutic strategies better tailored to minimizing the dose-limiting effect of ADR.

Keywords

Adriamycin doxorubicin mitochondria reactive oxygen species cardiac mtDNA 

Abbreviations

ADR

Adriamycin

ROS

reactive oxygen species

ETC

electron transport chain

CHF

congestive heart failure

ER

endoplasmic reticulum

MPT

mitochondrial permeability transition

ANT

adenine nucleotide transporter

8OHdG

8-hydroxydeoxyguanosine

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Toxicology Graduate Program, Medical SchoolUniversity of MinnesotaDuluthUSA
  2. 2.255 Medical SchoolUniversity of MinnesotaDuluthUSA

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