Cytofluorescence localization and disposition of doxorubicin and doxorubicinol in rat cardiac tissue

Eur J Cancer Clin Oncol. 1988 Jul;24(7):1123-31. doi: 10.1016/0277-5379(88)90118-6.

Abstract

The localization of cardiac cytofluorescence and tissue levels of doxorubicin (DXR) and doxorubicinol (DXR-ol) were studied in rats treated with a single (9 mg/kg: 1-day study) or 3 weekly doses (3 mg/kg: 7-week study) of the compounds. A striking orange-red fluorescence was observed in cardiac cell nuclei from DXR 1-day rats, whilst heart cells from DXR-ol 1-day rats displayed a faint, diffuse fluorescence. Neither cardiac tissue from DXR nor from DXR-ol 7-week animals showed any drug-specific fluorescence. HPLC assay showed that in DXR 1-day rats the drug was concentrated in the heart, which also contained the endogenously produced DXR-ol. Plasma levels of DXR-ol were initially high in DXR-ol 1-day rats but rapidly decreased with time; cardiac levels of DXR-ol remained low. Hearts from DXR 7-week rats contained appreciable amounts of DXR and DXR-ol, while very low levels of DXR-ol were found in DXR-ol 7-week animals. The data correlated well with the ECG alterations recorded during the study, which were more severe in DXR- than in DXR-ol-treated rats. These results indicate that the lower tissue uptake of exogenously administered DXR-ol might explain its lower toxic cardiac potential compared with DXR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / chemically induced
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics*
  • Doxorubicin / toxicity
  • Electrocardiography
  • Female
  • Myocardium / analysis*
  • Rats
  • Rats, Inbred Strains

Substances

  • Doxorubicin
  • adriamycinol