Slow-Release Doxorubicin Pellets Generate Myocardial Cardiotoxic Changes in Mice Without Significant Systemic Toxicity

Bradley D. Allen*, Zhuoli Zhang, Nivedita K. Naresh, Sol Misener, Daniele Procissi, James Carr

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

An increasing volume of pre-clinical and clinical-translational research is attempting to identify novel biomarkers for improved diagnosis and risk-stratification of chemotherapy-induced cardiotoxicity. Most published animal models have employed weekly intraperitoneal injections of doxorubicin to reach a desired cumulative dose. This approach can be associated with severe systemic toxicity which limits the animal model usefulness, particularly for advanced imaging. In the current study, slow-release subcutaneous doxorubicin pellets demonstrated histopathologic evidence of cardiotoxicity at doses similar to standard human dose-equivalents without limiting animal survival or ability to participate in advanced imaging studies. This approach may provide a more robust cardiotoxicity animal model.

Original languageEnglish (US)
JournalCardiovascular Toxicology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Doxorubicin
Toxicity
Animals
Animal Models
Translational Medical Research
Intraperitoneal Injections
Imaging techniques
Chemotherapy
Biomarkers
Drug Therapy
Cardiotoxicity

Keywords

  • Animal model
  • Cardio-oncology
  • Cardiotoxicity
  • Chemotherapy

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine

Cite this

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abstract = "An increasing volume of pre-clinical and clinical-translational research is attempting to identify novel biomarkers for improved diagnosis and risk-stratification of chemotherapy-induced cardiotoxicity. Most published animal models have employed weekly intraperitoneal injections of doxorubicin to reach a desired cumulative dose. This approach can be associated with severe systemic toxicity which limits the animal model usefulness, particularly for advanced imaging. In the current study, slow-release subcutaneous doxorubicin pellets demonstrated histopathologic evidence of cardiotoxicity at doses similar to standard human dose-equivalents without limiting animal survival or ability to participate in advanced imaging studies. This approach may provide a more robust cardiotoxicity animal model.",
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AU - Procissi, Daniele

AU - Carr, James

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AB - An increasing volume of pre-clinical and clinical-translational research is attempting to identify novel biomarkers for improved diagnosis and risk-stratification of chemotherapy-induced cardiotoxicity. Most published animal models have employed weekly intraperitoneal injections of doxorubicin to reach a desired cumulative dose. This approach can be associated with severe systemic toxicity which limits the animal model usefulness, particularly for advanced imaging. In the current study, slow-release subcutaneous doxorubicin pellets demonstrated histopathologic evidence of cardiotoxicity at doses similar to standard human dose-equivalents without limiting animal survival or ability to participate in advanced imaging studies. This approach may provide a more robust cardiotoxicity animal model.

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