Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy

Laura A.A. Gilliam, Jennifer S. Moylan, Leigh Ann Callahan, Marius P. Sumandea, Michael B. Reid

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Doxorubicin is a chemotherapeutic agent prescribed for a variety of tumors. While undergoing treatment, patients exhibit frequent symptoms that suggest respiratory muscle weakness. Cancer patients can receive doxorubicin chemotherapy through either intravenous (IV) or intraperitoneal (IP) injections. We hypothesized that respiratory muscle function would be depressed in a murine model of chemotherapy. We tested this hypothesis by treating C57BL/6 mice with a clinical dose of doxorubicin (20 mg/kg) via IV or IP injection. Three days later we measured contractile properties of muscle fiber bundles isolated from the diaphragm. Doxorubicin consistently depressed diaphragm force with both methods of administration (P < 0.01). Doxorubicin IP exaggerated the depression in diaphragm force and stimulated tissue inflammation and muscle fiber injury. These results suggest that clinically relevant doses of doxorubicin cause respiratory muscle weakness and that the loss of function depends, in part, on the route of administration. Muscle Nerve 43:94-102, 2011

Original languageEnglish
Pages (from-to)94-102
Number of pages9
JournalMuscle and Nerve
Volume43
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Chemotherapy
  • Inflammation
  • Oxidative stress
  • Respiratory muscle
  • Weakness

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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